{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:25:04Z","timestamp":1791919504236,"version":"4.3.4"},"reference-count":190,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["21588"],"award-info":[{"award-number":["21588"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Immunotherapy is presently one of the most promising areas of investigation and development for the treatment of cancer. While immune checkpoint-blocking monoclonal antibodies and chimeric antigen receptor (CAR) T-cell-based therapy have recently provided in some cases valuable therapeutic options, the goal of cure has not yet been achieved for most malignancies and more efforts are urgently needed. Noncoding RNAs (ncRNA), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), regulate several biological processes via selective targeting of crucial molecular signaling pathways. Recently, the key roles of miRNA and lncRNAs as regulators of the immune-response in cancer have progressively emerged, since they may act (i) by shaping the intrinsic tumor cell and microenvironment (TME) properties; (ii) by regulating angiogenesis, immune-escape, epithelial-to-mesenchymal transition, invasion, and drug resistance; and (iii) by acting as potential biomarkers for prognostic assessment and prediction of response to immunotherapy. In this review, we provide an overview on the role of ncRNAs in modulating the immune response and the TME. We discuss the potential use of ncRNAs as potential biomarkers or as targets for development or clinical translation of new therapeutics. Finally, we discuss the potential combinatory approaches based on ncRNA targeting agents and tumor immune-checkpoint inhibitor antibodies or CAR-T for the experimental treatment of human cancer.<\/jats:p>","DOI":"10.3390\/cancers13071587","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T09:57:04Z","timestamp":1617098224000},"page":"1587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["miRNAs and lncRNAs as Novel Therapeutic Targets to Improve Cancer Immunotherapy"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8205-2706","authenticated-orcid":false,"given":"Maria Teresa","family":"Di Martino","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7983-5099","authenticated-orcid":false,"given":"Caterina","family":"Riillo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8149-7957","authenticated-orcid":false,"given":"Francesca","family":"Scionti","sequence":"additional","affiliation":[{"name":"Institute of Research and Biomedical Innovation (IRIB), Italian National Council (CNR), 98164 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0268-5536","authenticated-orcid":false,"given":"Katia","family":"Grillone","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Poler\u00e0","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Caracciolo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariamena","family":"Arbitrio","sequence":"additional","affiliation":[{"name":"Institute of Research and Biomedical Innovation (IRIB), Italian National Council (CNR), 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierosandro","family":"Tagliaferri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierfrancesco","family":"Tassone","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41571-018-0142-8","article-title":"Cancer immunoediting and resistance to T cell-based immunotherapy","volume":"16","author":"Teng","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","article-title":"Oncology meets immunology: The cancer-immunity cycle","volume":"39","author":"Chen","year":"2013","journal-title":"Immunity"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.3389\/fimmu.2019.02965","article-title":"The Intriguing History of Cancer Immunotherapy","volume":"10","author":"Dobosz","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12472","DOI":"10.18632\/oncotarget.2998","article-title":"Classification of current anticancer immunotherapies","volume":"5","author":"Galluzzi","year":"2014","journal-title":"Oncotarget"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/nrg2083","article-title":"Genome-wide transcription and the implications for genomic organization","volume":"8","author":"Kapranov","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1021\/acschembio.8b00807","article-title":"Selective Small-Molecule Targeting of a Triple Helix Encoded by the Long Noncoding RNA, MALAT1","volume":"14","author":"Abulwerdi","year":"2019","journal-title":"ACS Chem. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1126\/science.1112014","article-title":"The transcriptional landscape of the mammalian genome","volume":"309","author":"Carninci","year":"2005","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e103777","DOI":"10.15252\/embj.2019103777","article-title":"A guide to naming human non-coding RNA genes","volume":"39","author":"Seal","year":"2020","journal-title":"EMBO J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.tig.2005.03.007","article-title":"Non-coding RNAs: Hope or hype?","volume":"21","author":"Huttenhofer","year":"2005","journal-title":"Trends Genet. TIG"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17719","DOI":"10.1073\/pnas.0703890104","article-title":"Genomic analysis of human microRNA transcripts","volume":"104","author":"Saini","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.cell.2009.01.035","article-title":"Origins and Mechanisms of miRNAs and siRNAs","volume":"136","author":"Carthew","year":"2009","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nature05983","article-title":"Intronic microRNA precursors that bypass Drosha processing","volume":"448","author":"Ruby","year":"2007","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1261\/rna.5167604","article-title":"Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs","volume":"10","author":"Bohnsack","year":"2004","journal-title":"RNA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1126\/science.1062961","article-title":"A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA","volume":"293","author":"Hutvagner","year":"2001","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/nsmb.1630","article-title":"Structural determinants of miRNAs for RISC loading and slicer-independent unwinding","volume":"16","author":"Kawamata","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/srep00996","article-title":"Stability of miRNA 5\u2019terminal and seed regions is correlated with experimentally observed miRNA-mediated silencing efficacy","volume":"2","author":"Hibio","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cell.2007.12.024","article-title":"Getting to the root of miRNA-mediated gene silencing","volume":"132","author":"Eulalio","year":"2008","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1126\/science.1149460","article-title":"Switching from repression to activation: microRNAs can up-regulate translation","volume":"318","author":"Vasudevan","year":"2007","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1161\/CIRCGENETICS.110.958363","article-title":"Circulating microRNAs as biomarkers and potential paracrine mediators of cardiovascular disease","volume":"3","author":"Gupta","year":"2010","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1093\/cvr\/cvu039","article-title":"Regulatory RNAs and paracrine networks in the heart","volume":"102","author":"Viereck","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"ref_21","first-page":"127","article-title":"Long non-coding RNAs: Versatile master regulators of gene expression and crucial players in cancer","volume":"4","author":"Nie","year":"2012","journal-title":"Am. J. Transl. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ygeno.2008.11.009","article-title":"Long intronic noncoding RNA transcription: Expression noise or expression choice?","volume":"93","author":"Louro","year":"2009","journal-title":"Genomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.cell.2009.02.006","article-title":"Evolution and functions of long noncoding RNAs","volume":"136","author":"Ponting","year":"2009","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1101\/gr.132159.111","article-title":"The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression","volume":"22","author":"Derrien","year":"2012","journal-title":"Genome Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1083\/jcb.200906113","article-title":"Paraspeckles: Nuclear bodies built on long noncoding RNA","volume":"186","author":"Bond","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/nature07672","article-title":"Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals","volume":"458","author":"Guttman","year":"2009","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"19202","DOI":"10.1073\/pnas.1217338109","article-title":"Formation of triple-helical structures by the 3\u2019-end sequences of MALAT1 and MENbeta noncoding RNAs","volume":"109","author":"Brown","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1261\/rna.029405.111","article-title":"Long noncoding RNAs are generated from the mitochondrial genome and regulated by nuclear-encoded proteins","volume":"17","author":"Rackham","year":"2011","journal-title":"RNA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nrg2521","article-title":"Long non-coding RNAs: Insights into functions","volume":"10","author":"Mercer","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_30","first-page":"181","article-title":"Functional Analysis of microRNA in Multiple Myeloma","volume":"1375","author":"Amodio","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3892\/or.2016.5236","article-title":"Non-coding RNAs as regulators in epigenetics (Review)","volume":"37","author":"Wei","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/j.cell.2013.02.016","article-title":"X-inactivation, imprinting, and long noncoding RNAs in health and disease","volume":"152","author":"Lee","year":"2013","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/415810a","article-title":"The non-coding Air RNA is required for silencing autosomal imprinted genes","volume":"415","author":"Sleutels","year":"2002","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nrg3606","article-title":"Long non-coding RNAs: New players in cell differentiation and development","volume":"15","author":"Fatica","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.4161\/rna.26165","article-title":"The long non-coding RNA Fendrr links epigenetic control mechanisms to gene regulatory networks in mammalian embryogenesis","volume":"10","author":"Grote","year":"2013","journal-title":"RNA Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.tig.2015.02.002","article-title":"Long noncoding RNAs in organogenesis: Making the difference","volume":"31","author":"Grote","year":"2015","journal-title":"Trends Genet. TIG"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"979","DOI":"10.4161\/rna.29937","article-title":"Decoding the noncoding: Prospective of lncRNA-mediated innate immune regulation","volume":"11","author":"Li","year":"2014","journal-title":"RNA Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2174\/2211536606666170117112322","article-title":"ImmunemiR\u2014A Database of Prioritized Immune miRNA Disease Associations and its Interactome","volume":"6","author":"Prabahar","year":"2017","journal-title":"MicroRNA"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wang, S., Zhou, S., Liu, H., Meng, Q., Ma, X., Liu, H., Wang, L., and Jiang, W. (2020). ncRI: A manually curated database for experimentally validated non-coding RNAs in inflammation. BMC Genom., 21.","DOI":"10.1186\/s12864-020-06794-6"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s12935-020-01242-7","article-title":"Bioinformatics profiling integrating a three immune-related long non-coding RNA signature as a prognostic model for clear cell renal cell carcinoma","volume":"20","author":"Jiang","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Xia, P., Li, Q., Wu, G., and Huang, Y. (2020). An Immune-Related lncRNA Signature to Predict Survival In Glioma Patients. Cell. Mol. Neurobiol.","DOI":"10.1007\/s10571-020-00857-8"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1038\/s41467-020-14802-2","article-title":"Pan-cancer characterization of immune-related lncRNAs identifies potential oncogenic biomarkers","volume":"11","author":"Li","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chen, T., Zhang, C., Liu, Y., Zhao, Y., Lin, D., Hu, Y., Yu, J., and Li, G. (2019). A gastric cancer LncRNAs model for MSI and survival prediction based on support vector machine. BMC Genom., 20.","DOI":"10.1186\/s12864-019-6135-x"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41392-020-0194-y","article-title":"Noncoding RNAs: The shot callers in tumor immune escape","volume":"5","author":"Liu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1158\/1078-0432.CCR-14-1860","article-title":"Immune escape mechanisms as a guide for cancer immunotherapy","volume":"21","author":"Beatty","year":"2015","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Lee, M.Y., Jeon, J.W., Sievers, C., and Allen, C.T. (2020). Antigen processing and presentation in cancer immunotherapy. J. Immunother. Cancer, 8.","DOI":"10.1136\/jitc-2020-001111"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e2120","DOI":"10.1038\/cddis.2016.28","article-title":"Proteomic screening identifies calreticulin as a miR-27a direct target repressing MHC class I cell surface exposure in colorectal cancer","volume":"7","author":"Colangelo","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1053\/j.gastro.2018.06.030","article-title":"microRNA 125a Regulates MHC-I Expression on Esophageal Adenocarcinoma Cells, Associated With Suppression of Antitumor Immune Response and Poor Outcomes of Patients","volume":"155","author":"Mari","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lazaridou, M.F., Massa, C., Handke, D., Mueller, A., Friedrich, M., Subbarayan, K., Tretbar, S., Dummer, R., Koelblinger, P., and Seliger, B. (2020). Identification of microRNAs Targeting the Transporter Associated with Antigen Processing TAP1 in Melanoma. J. Clin. Med., 9.","DOI":"10.3390\/jcm9092690"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s13045-018-0648-7","article-title":"Emerging roles of long non-coding RNAs in tumor metabolism","volume":"11","author":"Sun","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.canlet.2018.07.016","article-title":"LncRNA-p23154 promotes the invasion-metastasis potential of oral squamous cell carcinoma by regulating Glut1-mediated glycolysis","volume":"434","author":"Wang","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11010-019-03647-z","article-title":"Long non-coding RNA LINC00504 regulates the Warburg effect in ovarian cancer through inhibition of miR-1244","volume":"464","author":"Liu","year":"2020","journal-title":"Mol. Cell. Biochem."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ortiz-Pedraza, Y., Munoz-Bello, J.O., Olmedo-Nieva, L., Contreras-Paredes, A., Martinez-Ramirez, I., Langley, E., and Lizano, M. (2020). Non-Coding RNAs as Key Regulators of Glutaminolysis in Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082872"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1186\/s13046-018-0993-y","article-title":"Novel role of miR-133a-3p in repressing gastric cancer growth and metastasis via blocking autophagy-mediated glutaminolysis","volume":"37","author":"Zhang","year":"2018","journal-title":"J. Exp. Clin. Cancer Res. CR"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1002\/jcb.25927","article-title":"Long Non-Coding RNA MALAT1 Promotes Proliferation, Angiogenesis, and Immunosuppressive Properties of Mesenchymal Stem Cells by Inducing VEGF and IDO","volume":"118","author":"Li","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41573-018-0007-y","article-title":"Approaches to treat immune hot, altered and cold tumours with combination immunotherapies","volume":"18","author":"Galon","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12943-020-01154-0","article-title":"Noncoding RNAs in cancer immunity: Functions, regulatory mechanisms, and clinical application","volume":"19","author":"Zhang","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Xu, S.J., Hu, H.T., Li, H.L., and Chang, S. (2019). The Role of miRNAs in Immune Cell Development, Immune Cell Activation, and Tumor Immunity: With a Focus on Macrophages and Natural Killer Cells. Cells, 8.","DOI":"10.3390\/cells8101140"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3389\/fonc.2020.00048","article-title":"Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment","volume":"10","author":"Luo","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.18632\/oncotarget.1747","article-title":"Targeting of multiple myeloma-related angiogenesis by miR-199a-5p mimics: In vitro and in vivo anti-tumor activity","volume":"5","author":"Raimondi","year":"2014","journal-title":"Oncotarget"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/leu.2017.336","article-title":"MiR-29b antagonizes the pro-inflammatory tumor-promoting activity of multiple myeloma-educated dendritic cells","volume":"32","author":"Botta","year":"2018","journal-title":"Leukemia"},{"key":"ref_62","first-page":"405","article-title":"Tumor microenvironment and noncoding RNAs as co-drivers of epithelial-mesenchymal transition and cancer metastasis","volume":"247","author":"Meseure","year":"2018","journal-title":"Dev. Dyn. Off. Publ. Am. Assoc. Anat."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/cr.2015.51","article-title":"Epigenetic silencing of microRNA-149 in cancer-associated fibroblasts mediates prostaglandin E2\/interleukin-6 signaling in the tumor microenvironment","volume":"25","author":"Li","year":"2015","journal-title":"Cell Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.biopha.2015.08.013","article-title":"miR-101 represses lung cancer by inhibiting interaction of fibroblasts and cancer cells by down-regulating CXCL12","volume":"74","author":"Zhang","year":"2015","journal-title":"Biomed. Pharmacother. Biomed. Pharmacother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41416-019-0566-7","article-title":"MicroRNA-222 reprogrammed cancer-associated fibroblasts enhance growth and metastasis of breast cancer","volume":"121","author":"Chatterjee","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Di Martino, M.T., Campani, V., Misso, G., Gallo Cantafio, M.E., Gulla, A., Foresta, U., Guzzi, P.H., Castellano, M., Grimaldi, A., and Gigantino, V. (2014). In vivo activity of miR-34a mimics delivered by stable nucleic acid lipid particles (SNALPs) against multiple myeloma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090005"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1158\/1078-0432.CCR-15-0489","article-title":"A 13 mer LNA-i-miR-221 Inhibitor Restores Drug Sensitivity in Melphalan-Refractory Multiple Myeloma Cells","volume":"22","author":"Gulla","year":"2016","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Gallo Cantafio, M.E., Nielsen, B.S., Mignogna, C., Arbitrio, M., Botta, C., Frandsen, N.M., Rolfo, C., Tagliaferri, P., Tassone, P., and Di Martino, M.T. (2016). Pharmacokinetics and Pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in Mice and Non-human Primates. Mol. Ther. Nucleic Acids, 5.","DOI":"10.1038\/mtna.2016.36"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Di Martino, M.T., Arbitrio, M., Fonsi, M., Erratico, C.A., Scionti, F., Caracciolo, D., Tagliaferri, P., and Tassone, P. (2019). Allometric Scaling Approaches for Predicting Human Pharmacokinetic of a Locked Nucleic Acid Oligonucleotide Targeting Cancer-Associated miR-221. Cancers, 12.","DOI":"10.3390\/cancers12010027"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.omtn.2020.01.036","article-title":"Dose-Finding Study and Pharmacokinetics Profile of the Novel 13-Mer Antisense miR-221 Inhibitor in Sprague-Dawley Rats","volume":"20","author":"Arbitrio","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"242","DOI":"10.18632\/oncotarget.820","article-title":"In vitro and in vivo anti-tumor activity of miR-221\/222 inhibitors in multiple myeloma","volume":"4","author":"Gulla","year":"2013","journal-title":"Oncotarget"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s13046-018-0767-6","article-title":"miR-221 stimulates breast cancer cells and cancer-associated fibroblasts (CAFs) through selective interference with the A20\/c-Rel\/CTGF signaling","volume":"37","author":"Santolla","year":"2018","journal-title":"J. Exp. Clin. Cancer Res. CR"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13046-018-0995-9","article-title":"Downregulation of miRNA-214 in cancer-associated fibroblasts contributes to migration and invasion of gastric cancer cells through targeting FGF9 and inducing EMT","volume":"38","author":"Wang","year":"2019","journal-title":"J. Exp. Clin. Cancer Res. CR"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1111\/cas.14350","article-title":"Expression of long noncoding RNAs in cancer-associated fibroblasts linked to patient survival in ovarian cancer","volume":"111","author":"Colvin","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/carcin\/bgy006","article-title":"A novel stromal lncRNA signature reprograms fibroblasts to promote the growth of oral squamous cell carcinoma via LncRNA-CAF\/interleukin-33","volume":"39","author":"Ding","year":"2018","journal-title":"Carcinogenesis"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.molonc.2016.08.005","article-title":"Autophagy inhibition upregulates CD4(+) tumor infiltrating lymphocyte expression via miR-155 regulation and TRAIL activation","volume":"10","author":"Zarogoulidis","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"15179","DOI":"10.1038\/srep15179","article-title":"Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: A systematic review and meta-analysis","volume":"5","author":"Shang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/s41423-018-0004-4","article-title":"When worlds collide: Th17 and Treg cells in cancer and autoimmunity","volume":"15","author":"Knochelmann","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.3389\/fimmu.2020.02185","article-title":"The Role of MicroRNAs in Development and Function of Regulatory T Cells\u2014Lessons for a Better Understanding of MicroRNA Biology","volume":"11","author":"Krueger","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.3389\/fimmu.2018.01989","article-title":"The Long Non-coding RNA Flatr Anticipates Foxp3 Expression in Regulatory T Cells","volume":"9","author":"Brajic","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"27343","DOI":"10.18632\/oncotarget.4398","article-title":"Inhibition of miR-21 restores RANKL\/OPG ratio in multiple myeloma-derived bone marrow stromal cells and impairs the resorbing activity of mature osteoclasts","volume":"6","author":"Pitari","year":"2015","journal-title":"Oncotarget"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e511","DOI":"10.1038\/bcj.2016.118","article-title":"A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival","volume":"6","author":"Botta","year":"2016","journal-title":"Blood Cancer J."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Rossi, M., Altomare, E., Botta, C., Gallo Cantafio, M.E., Sarvide, S., Caracciolo, D., Riillo, C., Gaspari, M., Taverna, D., and Conforti, F. (2020). miR-21 antagonism abrogates Th17 tumor promoting functions in multiple myeloma. Leukemia.","DOI":"10.1038\/s41375-020-0947-1"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.3389\/fimmu.2019.01799","article-title":"Ontogeny of Tumor-Associated Macrophages","volume":"10","author":"Laviron","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12943-021-01313-x","article-title":"Non-coding RNAs regulation of macrophage polarization in cancer","volume":"20","author":"Mohapatra","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1007\/s00262-020-02511-0","article-title":"LincRNA-p21 knockdown reversed tumor-associated macrophages function by promoting MDM2 to antagonize* p53 activation and alleviate breast cancer development","volume":"69","author":"Zhou","year":"2020","journal-title":"Cancer Immunol. Immunother. CII"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3826","DOI":"10.1038\/s41467-018-06152-x","article-title":"LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment","volume":"9","author":"Chen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1038\/s41467-019-08989-2","article-title":"Apoptotic tumor cell-derived microRNA-375 uses CD36 to alter the tumor-associated macrophage phenotype","volume":"10","author":"Frank","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.immuni.2015.06.023","article-title":"Out-of-Sequence Signal 3 Paralyzes Primary CD4(+) T-Cell-Dependent Immunity","volume":"43","author":"Sckisel","year":"2015","journal-title":"Immunity"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/s12943-019-1091-2","article-title":"Novel immune checkpoint targets: Moving beyond PD-1 and CTLA-4","volume":"18","author":"Qin","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1093\/neuonc\/nov292","article-title":"MiR-138 exerts anti-glioma efficacy by targeting immune checkpoints","volume":"18","author":"Wei","year":"2016","journal-title":"Neuro-Oncology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"18530","DOI":"10.1074\/jbc.M117.808121","article-title":"Antitumor immunity is defective in T cell-specific microRNA-155-deficient mice and is rescued by immune checkpoint blockade","volume":"292","author":"Huffaker","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1158\/2159-8290.CD-16-1223","article-title":"Primary Resistance to PD-1 Blockade Mediated by JAK1\/2 Mutations","volume":"7","author":"Shin","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"13110","DOI":"10.1038\/srep13110","article-title":"Development of PD-1\/PD-L1 Pathway in Tumor Immune Microenvironment and Treatment for Non-Small Cell Lung Cancer","volume":"5","author":"He","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Cortez, M.A., Ivan, C., Valdecanas, D., Wang, X., Peltier, H.J., Ye, Y., Araujo, L., Carbone, D.P., Shilo, K., and Giri, D.K. (2016). PDL1 Regulation by p53 via miR-34. J. Natl. Cancer Inst., 108.","DOI":"10.1093\/jnci\/djv303"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1158\/0008-5472.CAN-18-1397","article-title":"miR-146a Controls Immune Response in the Melanoma Microenvironment","volume":"79","author":"Mastroianni","year":"2019","journal-title":"Cancer Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"39001","DOI":"10.18632\/oncotarget.16545","article-title":"Co-expression of AFAP1-AS1 and PD-1 predicts poor prognosis in nasopharyngeal carcinoma","volume":"8","author":"Tang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/s41577-019-0224-6","article-title":"TIM3 comes of age as an inhibitory receptor","volume":"20","author":"Wolf","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/s41419-018-0528-7","article-title":"Long non-coding RNA Lnc-Tim3 exacerbates CD8 T cell exhaustion via binding to Tim-3 and inducing nuclear translocation of Bat3 in HCC","volume":"9","author":"Ji","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/ni944","article-title":"BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1","volume":"4","author":"Watanabe","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_101","first-page":"89","article-title":"B and T Lymphocyte Attenuator is a Target of miR-155 during Naive CD4+ T Cell Activation","volume":"13","author":"Liu","year":"2016","journal-title":"Iran. J. Immunol. IJI"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/s41467-017-01062-w","article-title":"Resistance to checkpoint blockade therapy through inactivation of antigen presentation","volume":"8","author":"Jiao","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1093\/annonc\/mdw217","article-title":"Immune escape to PD-L1\/PD-1 blockade: Seven steps to success (or failure)","volume":"27","author":"Kim","year":"2016","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.it.2014.07.005","article-title":"Long non-coding RNAs in the regulation of the immune response","volume":"35","author":"Heward","year":"2014","journal-title":"Trends Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biocel.2019.01.019","article-title":"Repression of lncRNA NEAT1 enhances the antitumor activity of CD8(+)T cells against hepatocellular carcinoma via regulating miR-155\/Tim-3","volume":"110","author":"Yan","year":"2019","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/s41590-019-0400-7","article-title":"Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression","volume":"20","author":"Hu","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nature24627","article-title":"Structure of the human MHC-I peptide-loading complex","volume":"551","author":"Blees","year":"2017","journal-title":"Nature"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.semcancer.2007.07.004","article-title":"Soluble HLA-G: Are they clinically relevant?","volume":"17","author":"Pistoia","year":"2007","journal-title":"Semin. Cancer Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"59704","DOI":"10.18632\/oncotarget.10923","article-title":"IRES-dependent translation of the long non coding RNA meloe in melanoma cells produces the most immunogenic MELOE antigens","volume":"7","author":"Charpentier","year":"2016","journal-title":"Oncotarget"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"7501","DOI":"10.18632\/oncotarget.23483","article-title":"MALAT1\/miR-101-3p\/MCL1 axis mediates cisplatin resistance in lung cancer","volume":"9","author":"Wang","year":"2018","journal-title":"Oncotarget"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1002\/cam4.1384","article-title":"Long noncoding RNA MALAT1 knockdown reverses chemoresistance to temozolomide via promoting microRNA-101 in glioblastoma","volume":"7","author":"Cai","year":"2018","journal-title":"Cancer Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1200\/JCO.2006.09.4565","article-title":"Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection","volume":"25","author":"Gao","year":"2007","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1158\/2326-6066.CIR-18-0443","article-title":"The Pseudogene Olfr29-ps1 Promotes the Suppressive Function and Differentiation of Monocytic MDSCs","volume":"7","author":"Shang","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.4049\/jimmunol.1701721","article-title":"Lnc-chop Promotes Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Tumor and Inflammatory Environments","volume":"200","author":"Gao","year":"2018","journal-title":"J. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"15818","DOI":"10.1038\/ncomms15818","article-title":"Ash1l and lnc-Smad3 coordinate Smad3 locus accessibility to modulate iTreg polarization and T cell autoimmunity","volume":"8","author":"Xia","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_116","first-page":"2262","article-title":"Linc-POU3F3 promotes cell proliferation in gastric cancer via increasing T-reg distribution","volume":"7","author":"Xiong","year":"2015","journal-title":"Am. J. Transl. Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1146\/annurev-biochem-013118-111902","article-title":"Exosomes","volume":"88","author":"Pegtel","year":"2019","journal-title":"Annu. Rev. Biochem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"6105","DOI":"10.1038\/s41388-018-0391-0","article-title":"Primary tumor-derived exosomes facilitate metastasis by regulating adhesion of circulating tumor cells via SMAD3 in liver cancer","volume":"37","author":"Fu","year":"2018","journal-title":"Oncogene"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1158\/1078-0432.1010.11.3","article-title":"Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes","volume":"11","author":"Kim","year":"2005","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.imlet.2018.05.002","article-title":"Tumor exosomes block dendritic cells maturation to decrease the T cell immune response","volume":"199","author":"Ning","year":"2018","journal-title":"Immunol. Lett."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.trecan.2020.03.002","article-title":"Exosomal PD-L1: Roles in Tumor Progression and Immunotherapy","volume":"6","author":"Morrissey","year":"2020","journal-title":"Trends Cancer"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"15336","DOI":"10.1073\/pnas.1102855108","article-title":"Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma modulated by ATP-binding cassette transporter A3","volume":"108","author":"Aung","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/hep.30607","article-title":"Endoplasmic Reticulum Stress Causes Liver Cancer Cells to Release Exosomal miR-23a-3p and Up-regulate Programmed Death Ligand 1 Expression in Macrophages","volume":"70","author":"Liu","year":"2019","journal-title":"Hepatology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"5439","DOI":"10.18632\/oncotarget.2118","article-title":"Tumor-derived exosomes promote tumor progression and T-cell dysfunction through the regulation of enriched exosomal microRNAs in human nasopharyngeal carcinoma","volume":"5","author":"Ye","year":"2014","journal-title":"Oncotarget"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s00432-017-2361-2","article-title":"Exosomes-mediated transfer of long noncoding RNA ZFAS1 promotes gastric cancer progression","volume":"143","author":"Pan","year":"2017","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.bbrc.2017.06.055","article-title":"Serum long non coding RNA MALAT-1 protected by exosomes is up-regulated and promotes cell proliferation and migration in non-small cell lung cancer","volume":"490","author":"Zhang","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s12943-017-0714-8","article-title":"Hypoxic exosomes facilitate bladder tumor growth and development through transferring long non-coding RNA-UCA1","volume":"16","author":"Xue","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41392-020-0129-7","article-title":"Breast cancer-derived exosomes transmit lncRNA SNHG16 to induce CD73+gammadelta1 Treg cells","volume":"5","author":"Ni","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/s41419-019-2077-0","article-title":"LncRNA RPPH1 promotes colorectal cancer metastasis by interacting with TUBB3 and by promoting exosomes-mediated macrophage M2 polarization","volume":"10","author":"Liang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1158\/0008-5472.CAN-18-0014","article-title":"M2 Macrophage-Derived Exosomes Promote Cell Migration and Invasion in Colon Cancer","volume":"79","author":"Lan","year":"2019","journal-title":"Cancer Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrd.2016.246","article-title":"MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases","volume":"16","author":"Rupaimoole","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/nrd3179","article-title":"Targeting microRNAs in cancer: Rationale, strategies and challenges","volume":"9","author":"Garzon","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2174\/1389450117666160606104208","article-title":"Non Coding RNAs: A New Avenue for the Self-Tailoring of Blood Cancer Treatment","volume":"18","author":"Misso","year":"2017","journal-title":"Curr. Drug Targets"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"S125","DOI":"10.1517\/14712598.2013.796356","article-title":"Non-coding RNA: A novel opportunity for the personalized treatment of multiple myeloma","volume":"13","author":"Amodio","year":"2013","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.bbagrm.2011.05.014","article-title":"miRNA cassettes in viral vectors: Problems and solutions","volume":"1809","author":"Liu","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.addr.2014.10.031","article-title":"Recent progress in microRNA delivery for cancer therapy by non-viral synthetic vectors","volume":"81","author":"Wang","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Hutvagner, G., Simard, M.J., Mello, C.C., and Zamore, P.D. (2004). Sequence-specific inhibition of small RNA function. PLoS Biol., 2.","DOI":"10.1371\/journal.pbio.0020098"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"13233","DOI":"10.1021\/bi0485732","article-title":"LNA (locked nucleic acid): High-affinity targeting of complementary RNA and DNA","volume":"43","author":"Vester","year":"2004","journal-title":"Biochemistry"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1158\/1078-0432.CCR-12-3325","article-title":"Targeting miR-21 inhibits in vitro and in vivo multiple myeloma cell growth","volume":"19","author":"Leone","year":"2013","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nmeth1079","article-title":"MicroRNA sponges: Competitive inhibitors of small RNAs in mammalian cells","volume":"4","author":"Ebert","year":"2007","journal-title":"Nat. Methods"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1126\/science.1147535","article-title":"Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430","volume":"318","author":"Choi","year":"2007","journal-title":"Science"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"5633","DOI":"10.1073\/pnas.97.10.5633","article-title":"Potent and nontoxic antisense oligonucleotides containing locked nucleic acids","volume":"97","author":"Wahlestedt","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1182\/blood-2018-03-836601","article-title":"Therapeutic vulnerability of multiple myeloma to MIR17PTi, a first-in-class inhibitor of pri-miR-17-92","volume":"132","author":"Morelli","year":"2018","journal-title":"Blood"},{"key":"ref_144","first-page":"70","article-title":"Functional genomics: Screening for lncRNA function","volume":"18","author":"Koch","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Liu, S.J., Horlbeck, M.A., Cho, S.W., Birk, H.S., Malatesta, M., He, D., Attenello, F.J., Villalta, J.E., Cho, M.Y., and Chen, Y. (2017). CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells. Science, 355.","DOI":"10.1126\/science.aah7111"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/nm.4135","article-title":"p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity","volume":"22","author":"Adriaens","year":"2016","journal-title":"Nat. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1056\/NEJMcibr1603785","article-title":"Targeting a Long Noncoding RNA in Breast Cancer","volume":"374","author":"Mendell","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.7150\/ijbs.39768","article-title":"Axl-148b chimeric aptamers inhibit breast cancer and melanoma progression","volume":"16","author":"Quirico","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Kumar Kulabhusan, P., Hussain, B., and Yuce, M. (2020). Current Perspectives on Aptamers as Diagnostic Tools and Therapeutic Agents. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12070646"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.omtn.2019.10.021","article-title":"An Anti-BCMA RNA Aptamer for miRNA Intracellular Delivery","volume":"18","author":"Catuogno","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.cell.2012.09.042","article-title":"The loop position of shRNAs and pre-miRNAs is critical for the accuracy of dicer processing in vivo","volume":"151","author":"Gu","year":"2012","journal-title":"Cell"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/15476286.2015.1128062","article-title":"Quantitative evaluation of first, second, and third generation hairpin systems reveals the limit of mammalian vector-based RNAi","volume":"13","author":"Watanabe","year":"2016","journal-title":"RNA Biol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.chembiol.2016.05.021","article-title":"The Emerging Role of RNA as a Therapeutic Target for Small Molecules","volume":"23","author":"Connelly","year":"2016","journal-title":"Cell Chem. Biol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e1477","DOI":"10.1002\/wrna.1477","article-title":"Targeting RNA in mammalian systems with small molecules","volume":"9","author":"Donlic","year":"2018","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nrd.2018.93","article-title":"Principles for targeting RNA with drug-like small molecules","volume":"17","author":"Warner","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1073\/pnas.1914286117","article-title":"Small-molecule targeted recruitment of a nuclease to cleave an oncogenic RNA in a mouse model of metastatic cancer","volume":"117","author":"Costales","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"8880","DOI":"10.1021\/acs.jmedchem.9b01927","article-title":"How We Think about Targeting RNA with Small Molecules","volume":"63","author":"Costales","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.cell.2009.02.003","article-title":"The dynamic landscapes of RNA architecture","volume":"136","author":"Cruz","year":"2009","journal-title":"Cell"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1021\/ar200098t","article-title":"The molecular interactions that stabilize RNA tertiary structure: RNA motifs, patterns, and networks","volume":"44","author":"Butcher","year":"2011","journal-title":"Acc. Chem. Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.02.004","article-title":"RNA quaternary structure and global symmetry","volume":"40","author":"Jones","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ymeth.2018.03.009","article-title":"Adventures with RNA graphs","volume":"143","author":"Schlick","year":"2018","journal-title":"Methods"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.omtn.2017.06.005","article-title":"Therapeutic miRNA and siRNA: Moving from Bench to Clinic as Next Generation Medicine","volume":"8","author":"Chakraborty","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13046-020-01622-x","article-title":"Non-coding RNAs in cancer: Platforms and strategies for investigating the genomic \u201cdark matter\u201d","volume":"39","author":"Grillone","year":"2020","journal-title":"J. Exp. Clin. Cancer Res. CR"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1080\/17474086.2018.1517041","article-title":"The potential role of miRNAs in multiple myeloma therapy","volume":"11","author":"Caracciolo","year":"2018","journal-title":"Expert Rev. Hematol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1056\/NEJMoa1209026","article-title":"Treatment of HCV infection by targeting microRNA","volume":"368","author":"Janssen","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s10637-016-0407-y","article-title":"Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors","volume":"35","author":"Beg","year":"2017","journal-title":"Investig. New Drugs"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1042\/bj2530281","article-title":"A slow kinetic transient in RNA synthesis catalysed by wheat-germ RNA polymerase II","volume":"253","author":"Job","year":"1988","journal-title":"Biochem. J."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"217365","DOI":"10.1155\/2014\/217365","article-title":"Transferrin-conjugated SNALPs encapsulating 2\u2019-O-methylated miR-34a for the treatment of multiple myeloma","volume":"2014","author":"Scognamiglio","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.1038\/mtna.2014.47","article-title":"Mir-34: A new weapon against cancer?","volume":"3","author":"Misso","year":"2014","journal-title":"Mol. Ther. Nucleic acids"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"17949","DOI":"10.1038\/s41598-017-18186-0","article-title":"Evidence of novel miR-34a-based therapeutic approaches for multiple myeloma treatment","volume":"7","author":"Zarone","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"17579","DOI":"10.1038\/srep17579","article-title":"Delivery of miR-34a by chitosan\/PLGA nanoplexes for the anticancer treatment of multiple myeloma","volume":"5","author":"Cosco","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1016\/S1470-2045(17)30621-6","article-title":"Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: A first-in-man, phase 1, open-label, dose-escalation study","volume":"18","author":"Pavlakis","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ccr.2007.03.012","article-title":"Bacterially derived 400 nm particles for encapsulation and cancer cell targeting of chemotherapeutics","volume":"11","author":"MacDiarmid","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.21037\/tlcr.2017.12.01","article-title":"An innovative mesothelioma treatment based on miR-16 mimic loaded EGFR targeted minicells (TargomiRs)","volume":"7","author":"Viteri","year":"2018","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/bjh.15547","article-title":"Cobomarsen, an oligonucleotide inhibitor of miR-155, co-ordinately regulates multiple survival pathways to reduce cellular proliferation and survival in cutaneous T-cell lymphoma","volume":"183","author":"Seto","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"113451","DOI":"10.1016\/j.jpba.2020.113451","article-title":"Development and validation of bioanalytical methods for LNA-i-miR-221 quantification in human plasma and urine by LC-MS\/MS","volume":"188","author":"Franzoni","year":"2020","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jpba.2017.12.027","article-title":"Development and validation of a bioanalytical method for quantification of LNA-i-miR-221, a 13-mer oligonucleotide, in rat plasma using LC-MS\/MS","volume":"150","author":"Franzoni","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Di Martino, M.T., Gulla, A., Gallo Cantafio, M.E., Altomare, E., Amodio, N., Leone, E., Morelli, E., Lio, S.G., Caracciolo, D., and Rossi, M. (2014). In vitro and in vivo activity of a novel locked nucleic acid (LNA)-inhibitor-miR-221 against multiple myeloma cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089659"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1517\/14728222.2016.1164693","article-title":"Mir-221\/222 are promising targets for innovative anticancer therapy","volume":"20","author":"Rossi","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s41577-020-0275-8","article-title":"Dissecting the mechanisms of immune checkpoint therapy","volume":"20","author":"Sharma","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1200\/EDBK_240837","article-title":"Mechanisms of Resistance to Immune Checkpoint Blockade: Why Does Checkpoint Inhibitor Immunotherapy Not Work for All Patients?","volume":"39","author":"Fares","year":"2019","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_182","first-page":"114","article-title":"Identification of serum microRNAs predicting the response of esophageal squamous-cell carcinoma to nivolumab","volume":"50","author":"Sudo","year":"2020","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"e202149","DOI":"10.1001\/jamanetworkopen.2020.2149","article-title":"Association of Long Noncoding RNA Biomarkers with Clinical Immune Subtype and Prediction of Immunotherapy Response in Patients with Cancer","volume":"3","author":"Yu","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ebiom.2018.08.050","article-title":"Capturing functional long non-coding RNAs through integrating large-scale causal relations from gene perturbation experiments","volume":"35","author":"Xu","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"11406","DOI":"10.1038\/ncomms11406","article-title":"miR-424(322) reverses chemoresistance via T-cell immune response activation by blocking the PD-L1 immune checkpoint","volume":"7","author":"Xu","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"53735","DOI":"10.18632\/oncotarget.10731","article-title":"miR-28 modulates exhaustive differentiation of T cells through silencing programmed cell death-1 and regulating cytokine secretion","volume":"7","author":"Li","year":"2016","journal-title":"Oncotarget"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"7161","DOI":"10.1002\/cam4.2583","article-title":"MIR155HG is a prognostic biomarker and associated with immune infiltration and immune checkpoint molecules expression in multiple cancers","volume":"8","author":"Peng","year":"2019","journal-title":"Cancer Med."},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"Gallo Cantafio, M.E., Grillone, K., Caracciolo, D., Scionti, F., Arbitrio, M., Barbieri, V., Pensabene, L., Guzzi, P.H., and Di Martino, M.T. (2018). From Single Level Analysis to Multi-Omics Integrative Approaches: A Powerful Strategy towards the Precision Oncology. High-Throughput, 7.","DOI":"10.3390\/ht7040033"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13637-015-0023-8","article-title":"Analysis of miRNA, mRNA, and TF interactions through network-based methods","volume":"2015","author":"Guzzi","year":"2015","journal-title":"EURASIP J. Bioinform. Syst. Biol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"19132","DOI":"10.18632\/oncotarget.4302","article-title":"Integrated analysis of microRNAs, transcription factors and target genes expression discloses a specific molecular architecture of hyperdiploid multiple myeloma","volume":"6","author":"Guzzi","year":"2015","journal-title":"Oncotarget"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/7\/1587\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:10:27Z","timestamp":1760364627000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/7\/1587"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,30]]},"references-count":190,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["cancers13071587"],"URL":"https:\/\/doi.org\/10.3390\/cancers13071587","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,30]]}}}