{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:47:45Z","timestamp":1788583665112,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["19-14-00250"],"award-info":[{"award-number":["19-14-00250"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["19-74-30011"],"award-info":[{"award-number":["19-74-30011"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["FSUS-2020-0035"],"award-info":[{"award-number":["FSUS-2020-0035"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["19-14-00250"],"award-info":[{"award-number":["19-14-00250"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["19-74-30011"],"award-info":[{"award-number":["19-74-30011"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["FSUS-2020-0035"],"award-info":[{"award-number":["FSUS-2020-0035"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Rational combinations of sequence-specific inhibitors of pro-oncogenic miRNAs can efficiently interfere with specific tumor survival pathways, offering great promise for targeted therapy of oncological diseases. Herein, we uncovered the potential of multicomponent therapy by double or triple combinations of highly potent mesyl phosphoramidate (\u00b5) antisense oligodeoxynucleotides targeted to three proven pro-oncogenic microRNAs\u2014miR-17, miR-21, and miR-155. A strong synergism in the inhibition of proliferation and migration of B16 melanoma cells was demonstrated in vitro for pairs of \u00b5-oligonucleotides, which resulted in vivo in profound inhibition (up to 85%) of lung metastases development after intravenous injection of \u00b5-oligonucleotide-transfected B16 cells in mice. A clear benefit of \u00b5-21-ON\/\u00b5-17-ON and \u00b5-17-ON\/\u00b5-155-ON\/\u00b5-21-ON combination antitumor therapy was shown for the lymphosarcoma RLS40 solid tumor model. In vivo administration of the \u00b5-17-ON\/\u00b5-155-ON\/\u00b5-21-ON cocktail into RLS40-bearing mice elicited fourfold delay of tumor growth as a result of strong inhibition of tumor mitotic activity. It was discovered that the cocktail of \u00b5-21-ON\/\u00b5-17-ON\/\u00b5-155-ON led to a twofold decrease in total destructive changes in murine liver, which indicates both the reduction in toxic tumor burden and the absence of specific toxicity of the proposed therapy.<\/jats:p>","DOI":"10.3390\/cancers14184396","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T20:52:25Z","timestamp":1663015945000},"page":"4396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Single Shot vs. Cocktail: A Comparison of Mono- and Combinative Application of miRNA-Targeted Mesyl Oligonucleotides for Efficient Antitumor Therapy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7767-7712","authenticated-orcid":false,"given":"Svetlana","family":"Gaponova","sequence":"first","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev\u2019s Ave. 8, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Patutina","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev\u2019s Ave. 8, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5729-9910","authenticated-orcid":false,"given":"Aleksandra","family":"Sen\u2019kova","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev\u2019s Ave. 8, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Burakova","sequence":"additional","affiliation":[{"name":"Department of Physics, Novosibirsk State University, Pirogova Str. 1, Novosibirsk 630090, Russia"},{"name":"Sector of Plant Chemical Biology, Institute of Cytology and Genetics SB RAS, Lavrentiev Ave. 10, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3032-858X","authenticated-orcid":false,"given":"Innokenty","family":"Savin","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev\u2019s Ave. 8, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7569-9555","authenticated-orcid":false,"given":"Andrey","family":"Markov","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev\u2019s Ave. 8, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3727-4905","authenticated-orcid":false,"given":"Elena","family":"Shmendel","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Technology of Biologically Active Compounds, Medical and Organic Chemistry Named after N. A. Preobrazhensky, MIREA\u2013Russian Technological University, Vernadsky Ave. 78, Moscow 119454, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5372-1325","authenticated-orcid":false,"given":"Mikhail","family":"Maslov","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Technology of Biologically Active Compounds, Medical and Organic Chemistry Named after N. A. Preobrazhensky, MIREA\u2013Russian Technological University, Vernadsky Ave. 78, Moscow 119454, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5215-5704","authenticated-orcid":false,"given":"Dmitry","family":"Stetsenko","sequence":"additional","affiliation":[{"name":"Department of Physics, Novosibirsk State University, Pirogova Str. 1, Novosibirsk 630090, Russia"},{"name":"Sector of Plant Chemical Biology, Institute of Cytology and Genetics SB RAS, Lavrentiev Ave. 10, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Vlassov","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev\u2019s Ave. 8, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4044-1049","authenticated-orcid":false,"given":"Marina","family":"Zenkova","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev\u2019s Ave. 8, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.1002\/jcp.30276","article-title":"Signaling, Metabolism, and Cancer: An Important Relationship for Therapeutic Intervention","volume":"236","author":"Ferns","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mercatelli, N., Coppola, V., Bonci, D., Miele, F., Costantini, A., Guadagnoli, M., Bonanno, E., Muto, G., Frajese, G.V., and De Maria, R. (2008). The Inhibition of the Highly Expressed Mir-221 and Mir-222 Impairs the Growth of Prostate Carcinoma Xenografts in Mice. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0004029"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4973","DOI":"10.1093\/nar\/gkg707","article-title":"Developmental Defects by Antisense-Mediated Inactivation of Micro-RNAs 2 and 13 in Drosophila and the Identification of Putative Target Genes","volume":"31","author":"Boutla","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Raue, R., Frank, A.C., Syed, S.N., and Br\u00fcne, B. (2021). Therapeutic Targeting of Micrornas in the Tumor Microenvironment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042210"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13221-015-0031-1","article-title":"Therapeutic Manipulation of Angiogenesis with MiR-27b","volume":"7","author":"Veliceasa","year":"2015","journal-title":"Vasc. Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5006","DOI":"10.1038\/onc.2017.129","article-title":"MIR-181b Modulates EGFR-Dependent VCAM-1 Expression and Monocyte Adhesion in Glioblastoma","volume":"36","author":"Liu","year":"2017","journal-title":"Oncogene"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cyto.2016.01.015","article-title":"Sponges against MiR-19 and MiR-155 Reactivate the P53-Socs1 Axis in Hematopoietic Cancers","volume":"82","author":"Mignacca","year":"2016","journal-title":"Cytokine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"949","DOI":"10.3892\/mmr.2012.779","article-title":"MicroRNA-155 Silencing Inhibits Proliferation and Migration and Induces Apoptosis by Upregulating BACH1 in Renal Cancer Cells","volume":"5","author":"Li","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"371","DOI":"10.5732\/cjc.30.0371","article-title":"Apoptosis and the Target Genes of MicroRNA-21","volume":"30","author":"Buscaglia","year":"2011","journal-title":"Chin. J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6029","DOI":"10.1158\/0008-5472.CAN-05-0137","article-title":"MicroRNA-21 Is an Antiapoptotic Factor in Human Glioblastoma Cells","volume":"65","author":"Chan","year":"2005","journal-title":"Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.bbrc.2009.03.077","article-title":"MicroRNA-21 Directly Targets MARCKS and Promotes Apoptosis Resistance and Invasion in Prostate Cancer Cells","volume":"383","author":"Li","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"488","DOI":"10.3389\/fphar.2019.00488","article-title":"Enhanced Inhibition of Tumorigenesis Using Combinations of MiRNA-Targeted Therapeutics","volume":"10","author":"Miroshnichenko","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2017.05.007","article-title":"Chemosensitization and Inhibition of Pancreatic Cancer Stem Cell Proliferation by Overexpression of MicroRNA-205","volume":"402","author":"Chaudhary","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1111\/cas.13267","article-title":"Co-Delivery of MicroRNA-21 Antisense Oligonucleotides and Gemcitabine Using Nanomedicine for Pancreatic Cancer Therapy","volume":"108","author":"Li","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3547","DOI":"10.1038\/onc.2014.282","article-title":"A Combinatorial MicroRNA Therapeutics Approach to Suppressing Non-Small Cell Lung Cancer","volume":"34","author":"Kasinski","year":"2015","journal-title":"Oncogene"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13149","DOI":"10.18632\/oncotarget.3693","article-title":"MiR-497 and MiR-34a Retard Lung Cancer Growth by Co-Inhibiting Cyclin E1 (CCNE1)","volume":"6","author":"Han","year":"2015","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10507","DOI":"10.1007\/s13277-016-4937-x","article-title":"The Effect of Antisense Inhibitor of MiRNA 106b\u223c25 on the Proliferation, Invasion, Migration, and Apoptosis of Gastric Cancer Cell","volume":"37","author":"Zhang","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.3892\/ijo.2012.1542","article-title":"Co-Inhibition of MicroRNA-10b and MicroRNA-21 Exerts Synergistic Inhibition on the Proliferation and Invasion of Human Glioma Cells","volume":"41","author":"Dong","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1021\/acs.molpharmaceut.5b00756","article-title":"Combined Delivery of Let-7b MicroRNA and Paclitaxel via Biodegradable Nanoassemblies for the Treatment of KRAS Mutant Cancer","volume":"13","author":"Dai","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s13046-015-0216-8","article-title":"Dual Loading MiR-218 Mimics and Temozolomide Using AuCOOH@FA-CS Drug Delivery System: Promising Targeted Anti-Tumor Drug Delivery System with Sequential Release Functions","volume":"34","author":"Fan","year":"2015","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"668","DOI":"10.3892\/mmr.2015.3376","article-title":"MicroRNA-183\/182\/96 Cooperatively Regulates the Proliferation of Colon Cancer Cells","volume":"12","author":"Zhang","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_22","first-page":"1653","article-title":"Co-Suppression of MiR-221\/222 Cluster Suppresses Human Glioma Cell Growth by Targeting P27kip1 in Vitro and in Vivo","volume":"34","author":"Zhang","year":"2009","journal-title":"Int. J. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.3892\/ijo.2015.3308","article-title":"High Levels of Apoptosis Are Induced in Human Glioma Cell Lines by Co-Administration of Peptide Nucleic Acids Targeting MiR-221 and MiR-222","volume":"48","author":"Brognara","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1073\/pnas.1813376116","article-title":"Mesyl Phosphoramidate Antisense Oligonucleotides as an Alternative to Phosphorothioates with Improved Biochemical and Biological Properties","volume":"116","author":"Miroshnichenko","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"32370","DOI":"10.1073\/pnas.2016158117","article-title":"Mesyl Phosphoramidate Backbone Modified Antisense Oligonucleotides Targeting MiR-21 with Enhanced in Vivo Therapeutic Potency","volume":"117","author":"Patutina","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1089\/nat.2020.0860","article-title":"Mesyl Phosphoramidate Oligonucleotides as Potential Splice-Switching Agents: Impact of Backbone Structure on Activity and Intracellular Localization","volume":"31","author":"Hammond","year":"2021","journal-title":"Nucleic Acid Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9026","DOI":"10.1093\/nar\/gkab718","article-title":"Towards next Generation Antisense Oligonucleotides: Mesylphosphoramidate Modification Improves Therapeutic Index and Duration of Effect of Gapmer Antisense Oligonucleotides","volume":"49","author":"Anderson","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1196\/annals.1378.090","article-title":"Animal Model of Drug-Resistant Tumor Progression","volume":"1091","author":"Mironova","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"W488","DOI":"10.1093\/nar\/gkaa216","article-title":"SynergyFinder 2.0: Visual Analytics of Multi-Drug Combination Synergies","volume":"48","author":"Ianevski","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.biomaterials.2017.01.018","article-title":"MiRNases: Novel Peptide-Oligonucleotide Bioconjugates That Silence MiR-21 in Lymphosarcoma Cells","volume":"122","author":"Patutina","year":"2017","journal-title":"Biomaterials"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ejpb.2017.11.010","article-title":"Targeted Delivery of Nucleic Acids into Xenograft Tumors Mediated by Novel Folate-Equipped Liposomes","volume":"123","author":"Kabilova","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_32","first-page":"D148","article-title":"MiRTarBase 2020: Updates to the Experimentally Validated MicroRNA-Target Interaction Database","volume":"48","author":"Huang","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kutmon, M., Kelder, T., Mandaviya, P., Evelo, C.T.A., and Coort, S.L. (2013). CyTargetLinker: A Cytoscape App to Integrate Regulatory Interactions in Network Analysis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082160"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape Plug-in to Decipher Functionally Grouped Gene Ontology and Pathway Annotation Networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1021\/acs.jproteome.8b00702","article-title":"Cytoscape StringApp: Network Analysis and Visualization of Proteomics Data","volume":"18","author":"Doncheva","year":"2019","journal-title":"J. Proteome Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1093\/bioinformatics\/btm554","article-title":"Computing Topological Parameters of Biological Networks","volume":"24","author":"Assenov","year":"2008","journal-title":"Bioinformatics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-1-61779-123-9_10","article-title":"Quantitative Stem-Loop RT-PCR for Detection of MicroRNAs","volume":"Volume 744","author":"Hellens","year":"2011","journal-title":"Methods in Molecular Biology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e179","DOI":"10.1093\/nar\/gni178","article-title":"Real-Time Quantification of MicroRNAs by Stem-Loop RT-PCR","volume":"33","author":"Chen","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"14990","DOI":"10.1038\/s41598-018-33331-z","article-title":"Peptide-Oligonucleotide Conjugates Exhibiting Pyrimidine-X Cleavage Specificity Efficiently Silence MiRNA Target Acting Synergistically with RNase H","volume":"8","author":"Patutina","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s10616-021-00482-3","article-title":"MiR-17-5p Accelerates Cervical Cancer Cells Migration and Invasion via the TIMP2\/MMPs Signaling Cascade","volume":"73","author":"Zou","year":"2021","journal-title":"Cytotechnology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1111\/cas.12479","article-title":"SS18-SSX-Regulated MiR-17 Promotes Tumor Growth of Synovial Sarcoma by Inhibiting P21WAF1\/CIP1","volume":"105","author":"Minami","year":"2014","journal-title":"Cancer Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5768","DOI":"10.1111\/jcmm.13866","article-title":"The Novel Regulatory Role of LncRNA-MiRNA-MRNA Axis in Cardiovascular Diseases","volume":"22","author":"Huang","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"249","DOI":"10.4149\/neo_2019_190110N29","article-title":"MiR-17-5p Knockdown Inhibits Proliferation, Autophagy and Promotes Apoptosis in Thyroid Cancer via Targeting PTEN","volume":"67","author":"Shi","year":"2020","journal-title":"Neoplasma"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1089\/nat.2020.0914","article-title":"MiR-21: A Key Small Molecule with Great Effects in Combination Cancer Therapy","volume":"31","author":"Arghiani","year":"2021","journal-title":"Nucleic Acid Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s10555-017-9724-7","article-title":"MiR-155 in Cancer Drug Resistance and as Target for MiRNA-Based Therapeutics","volume":"37","author":"Bayraktar","year":"2018","journal-title":"Cancer Metastasis Rev."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Maga\u00f1a, A., and Blanco, F.J. (2020). Human PCNA Structure, Function, and Interactions. Biomolecules, 10.","DOI":"10.3390\/biom10040570"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Gladkikh, D.V., Sen\u2032 Kova, A.V., Chernikov, I.V., Kabilova, T.O., Popova, N.A., Nikolin, V.P., Shmendel, E.V., Maslov, M.A., Vlassov, V.V., and Zenkova, M.A. (2021). Folate-Equipped Cationic Liposomes Deliver Anti-Mdr1-Sirna to the Tumor and Increase the Efficiency of Chemotherapy. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13081252"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1517\/14712598.7.9.1363","article-title":"MicroRNA Expression in Lymphoma","volume":"7","author":"Lawrie","year":"2007","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8725","DOI":"10.1038\/ncomms9725","article-title":"MiR-17-92 Fine-Tunes MYC Expression and Function to Ensure Optimal B Cell Lymphoma Growth","volume":"6","author":"Mihailovich","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Haidar, M., and Jacquemin, P. (2021). Past and Future Strategies to Inhibit Membrane Localization of the KRAS Oncogene. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413193"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ymeth.2014.10.002","article-title":"Study of PTEN Subcellular Localization","volume":"77\u201378","author":"Bononi","year":"2015","journal-title":"Methods"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/nrm3330","article-title":"The Functions and Regulation of the PTEN Tumour Suppressor","volume":"13","author":"Song","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"415","DOI":"10.5483\/BMBRep.2019.52.7.152","article-title":"Highlighted STAT3 as a Potential Drug Target for Cancer Therapy","volume":"52","author":"Lee","year":"2019","journal-title":"BMB Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0092-8674(00)81959-5","article-title":"Stat3 as an Oncogene","volume":"98","author":"Bromberg","year":"1999","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1038\/s41418-021-00789-w","article-title":"Sorting Nexin 3 Induces Heart Failure via Promoting Retromer-Dependent Nuclear Trafficking of STAT3","volume":"28","author":"Lu","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00428-008-0617-6","article-title":"Expression and Intracellular Localization of Matrix Metalloproteinases in Intraductal Papillary Mucinous Neoplasms of the Pancreas","volume":"453","author":"Tamahashi","year":"2008","journal-title":"Virchows Arch."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"112260","DOI":"10.1016\/j.ejmech.2020.112260","article-title":"Matrix Metalloproteinase-9 (MMP-9) and Its Inhibitors in Cancer: A Minireview","volume":"194","author":"Mondal","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1095\/biolreprod.112.106989","article-title":"Ovarian Expression, Localization, and Function of Tissue Inhibitor of Metalloproteinase 3 (TIMP3) During the Periovulatory Period of the Human Menstrual Cycle","volume":"89","author":"Rosewell","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Tran, T.T., Rane, C.K., Zito, C.R., Weiss, S.A., Jessel, S., Lucca, L., Lu, B.Y., Oria, V.O., Adeniran, A., and Chiang, V.L. (2021). Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells. Cancers, 13.","DOI":"10.3390\/cancers13051049"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Pavlenko, E., Cabron, A.S., Arnold, P., Dobert, J.P., Rose-John, S., and Zunke, F. (2019). Functional Characterization of Colon Cancer-Associated Mutations in ADAM17: Modifications in the Pro-Domain Interfere with Trafficking and Maturation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092198"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"152410","DOI":"10.1016\/j.prp.2019.04.002","article-title":"The Metalloprotease ADAM17 in Inflammation and Cancer","volume":"215","author":"Lokau","year":"2019","journal-title":"Pathol. Res. Pract."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Saad, M.I., Rose-John, S., and Jenkins, B.J. (2019). ADAM17: An Emerging Therapeutic Target for Lung Cancer. Cancers, 11.","DOI":"10.3390\/cancers11091218"},{"key":"ref_63","first-page":"932","article-title":"Anti-Leukemia Mechanism of MiR-17 and MiR-20a Silencing Mediated by MiRNA Sponge","volume":"22","author":"Niu","year":"2014","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"47984","DOI":"10.18632\/oncotarget.18207","article-title":"Co-Targeting of IGF1R\/MTOR Pathway by MiR-497 and MiR-99a Impairs Hepatocellular Carcinoma Development","volume":"8","author":"Cheng","year":"2017","journal-title":"Oncotarget"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.biopha.2018.01.055","article-title":"MiR-204 Inhibits Angiogenesis and Promotes Sensitivity to Cetuximab in Head and Neck Squamous Cell Carcinoma Cells by Blocking JAK2-STAT3 Signaling","volume":"99","author":"Wu","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.1093\/nar\/gkn1053","article-title":"A Single Anti-MicroRNA Antisense Oligodeoxyribonucleotide (AMO) Targeting Multiple MicroRNAs Offers an Improved Approach for MicroRNA Interference","volume":"37","author":"Lu","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6099","DOI":"10.1038\/sj.onc.1210425","article-title":"Apoptosis Induction by Antisense Oligonucleotides against MiR-17-5p and MiR-20a in Lung Cancers Overexpressing MiR-17-92","volume":"26","author":"Matsubara","year":"2007","journal-title":"Oncogene"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s12943-015-0385-2","article-title":"Alterations in MicroRNAs MiR-21 and Let-7a Correlate with Aberrant STAT3 Signaling and Downstream Effects during Cervical Carcinogenesis","volume":"14","author":"Shishodia","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/mc.22542","article-title":"MicroRNA-21 Regulates the ERK\/NF-\u039aB Signaling Pathway to Affect the Proliferation, Migration, and Apoptosis of Human Melanoma A375 Cells by Targeting SPRY1, PDCD4, and PTEN","volume":"56","author":"Mao","year":"2017","journal-title":"Mol. Carcinog."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1136\/jclinpath-2021-208008","article-title":"PTEN as a Target in Melanoma","volume":"75","author":"Ince","year":"2022","journal-title":"J. Clin. Pathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.bbrc.2019.12.085","article-title":"BRAF V600E Dictates Cell Survival via C-Myc-Dependent Induction of Skp2 in Human Melanoma","volume":"524","author":"Feng","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/18\/4396\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:28:43Z","timestamp":1760142523000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/18\/4396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":71,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["cancers14184396"],"URL":"https:\/\/doi.org\/10.3390\/cancers14184396","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,9]]}}}