{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T01:10:48Z","timestamp":1772932248061,"version":"3.50.1"},"reference-count":84,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T00:00:00Z","timestamp":1730678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Science Foundation","award":["20-15-00368"],"award-info":[{"award-number":["20-15-00368"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Abstract: Our work aimed to evaluate and differentiate the role of ten lncRNA genes (GAS5, HAND2-AS1, KCNK15-AS1, MAGI2-AS3, MEG3, SEMA3B-AS1, SNHG6, SSTR5-AS1, ZEB1-AS1, and ZNF667-AS1) in the development and progression of epithelial ovarian cancer (EOC). A representative set of clinical samples was used: 140 primary tumors from patients without and with metastases and 59 peritoneal metastases. Using MS-qPCR, we demonstrated an increase in methylation levels of all ten lncRNA genes in tumors compared to normal tissues (p &lt; 0.001). Using RT-qPCR, we showed downregulation and an inverse relationship between methylation and expression levels for ten lncRNAs (rs &lt; \u22120.5). We further identified lncRNA genes that were specifically hypermethylated in tumors from patients with metastases to lymph nodes (HAND2-AS1), peritoneum (KCNK15-AS1, MEG3, and SEMA3B-AS1), and greater omentum (MEG3, SEMA3B-AS1, and ZNF667-AS1). The same four lncRNA genes involved in peritoneal spread were associated with clinical stage and tumor extent (p &lt; 0.001). Interestingly, we found a reversion from increase to decrease in the hypermethylation level of five metastasis-related lncRNA genes (MEG3, SEMA3B-AS1, SSTR5-AS1, ZEB1-AS1, and ZNF667-AS1) in 59 peritoneal metastases. This reversion may be associated with partial epithelial\u2013mesenchymal transition (EMT) in metastatic cells, as indicated by a decrease in the level of the EMT marker, CDH1 mRNA (p &lt; 0.01). Furthermore, novel mRNA targets and regulated miRNAs were predicted for a number of the studied lncRNAs using the NCBI GEO datasets and analyzed by RT-qPCR and transfection of SKOV3 and OVCAR3 cells. In addition, hypermethylation of SEMA3B-AS1, SSTR5-AS1, and ZNF667-AS1 genes was proposed as a marker for overall survival in patients with EOC.<\/jats:p>","DOI":"10.3390\/ijms252111843","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T09:52:54Z","timestamp":1730713974000},"page":"11843","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ten Hypermethylated lncRNA Genes Are Specifically Involved in the Initiation, Progression, and Lymphatic and Peritoneal Metastasis of Epithelial Ovarian Cancer"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-4094","authenticated-orcid":false,"given":"Eleonora A.","family":"Braga","sequence":"first","affiliation":[{"name":"Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9398-8075","authenticated-orcid":false,"given":"Alexey M.","family":"Burdennyy","sequence":"additional","affiliation":[{"name":"Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2878-5703","authenticated-orcid":false,"given":"Leonid A.","family":"Uroshlev","sequence":"additional","affiliation":[{"name":"Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danila M.","family":"Zaichenko","sequence":"additional","affiliation":[{"name":"Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7172-0433","authenticated-orcid":false,"given":"Elena A.","family":"Filippova","sequence":"additional","affiliation":[{"name":"Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6246-2444","authenticated-orcid":false,"given":"Svetlana S.","family":"Lukina","sequence":"additional","affiliation":[{"name":"Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0423-7801","authenticated-orcid":false,"given":"Irina V.","family":"Pronina","sequence":"additional","affiliation":[{"name":"Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3473-5453","authenticated-orcid":false,"given":"Iana R.","family":"Astafeva","sequence":"additional","affiliation":[{"name":"Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina V.","family":"Fridman","sequence":"additional","affiliation":[{"name":"Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana P.","family":"Kazubskaya","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vitaly I.","family":"Loginov","sequence":"additional","affiliation":[{"name":"Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6827-9584","authenticated-orcid":false,"given":"Alexey A.","family":"Dmitriev","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksey A.","family":"Moskovtsev","sequence":"additional","affiliation":[{"name":"Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia"},{"name":"N.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, Russia"},{"name":"Russian Medical Academy of Continuing Professional Education, 125993 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolay E.","family":"Kushlinskii","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"264","DOI":"10.5694\/mja2.52227","article-title":"Screening and prevention of ovarian cancer","volume":"220","author":"Sideris","year":"2024","journal-title":"Med. J. Aust."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41571-024-00881-3","article-title":"Global epidemiology of epithelial ovarian cancer","volume":"21","author":"Webb","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/S0140-6736(18)32552-2","article-title":"Epithelial ovarian cancer","volume":"393","author":"Lheureux","year":"2019","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pascual-Anton, L., Cardenes, B., Sainz de la Cuesta, R., Gonzalez-Cortijo, L., Lopez-Cabrera, M., Cabanas, C., and Sandoval, P. (2021). Mesothelial-to-Mesenchymal Transition and Exosomes in Peritoneal Metastasis of Ovarian Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111496"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5367","DOI":"10.7150\/jca.98409","article-title":"Research progress of epithelial-mesenchymal transformation-related transcription factors in peritoneal metastases","volume":"15","author":"Wang","year":"2024","journal-title":"J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s10555-012-9351-2","article-title":"Cell-cell and cell-matrix dynamics in intraperitoneal cancer metastasis","volume":"31","author":"Sodek","year":"2012","journal-title":"Cancer Metastasis Rev."},{"key":"ref_8","first-page":"1357","article-title":"Detachment from the primary site and suspension in ascites as the initial step in metabolic reprogramming and metastasis to the omentum in ovarian cancer","volume":"15","author":"Sato","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13048-021-00795-z","article-title":"Early stage epithelial ovarian cancer metastasis through peritoneal fluid circulation","volume":"14","author":"Purbadi","year":"2021","journal-title":"J. Ovarian Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ibrahim, L.I., Hajal, C., Offeddu, G.S., Gillrie, M.R., and Kamm, R.D. (2022). Omentum-on-a-chip: A multicellular, vascularized microfluidic model of the human peritoneum for the study of ovarian cancer metastases. Biomaterials, 288.","DOI":"10.1016\/j.biomaterials.2022.121728"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Miyamoto, T., Murphy, B., and Zhang, N. (2023). Intraperitoneal metastasis of ovarian cancer: New insights on resident macrophages in the peritoneal cavity. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1104694"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.cell.2011.07.014","article-title":"A ceRNA hypothesis: The Rosetta Stone of a hidden RNA language?","volume":"146","author":"Salmena","year":"2011","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.cell.2012.06.013","article-title":"Cancer epigenetics: From mechanism to therapy","volume":"150","author":"Dawson","year":"2012","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Alexandrova, A., and Lomakina, M. (2022). How does plasticity of migration help tumor cells to avoid treatment: Cytoskeletal regulators and potential markers. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.962652"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Garcia-Padilla, C., Duenas, A., Garcia-Lopez, V., Aranega, A., Franco, D., Garcia-Martinez, V., and Lopez-Sanchez, C. (2022). Molecular Mechanisms of lncRNAs in the Dependent Regulation of Cancer and Their Potential Therapeutic Use. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020764"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Braga, E.A., Fridman, M.V., Moscovtsev, A.A., Filippova, E.A., Dmitriev, A.A., and Kushlinskii, N.E. (2020). LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228855"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Yang, Z., Xu, F., Teschendorff, A.E., Zhao, Y., Yao, L., Li, J., and He, Y. (2022). Insights into the role of long non-coding RNAs in DNA methylation mediated transcriptional regulation. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.1067406"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1007\/s10517-021-05230-3","article-title":"Hypermethylation of Genes in New Long Noncoding RNA in Ovarian Tumors and Metastases: A Dual Effect","volume":"171","author":"Burdennyy","year":"2021","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s10517-024-06054-7","article-title":"DNA Methylation of a Group of Long Non-Coding RNA Genes at Different Stages of Ovarian Cancer Dissemination","volume":"176","author":"Burdennyy","year":"2024","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3892\/or.2014.3208","article-title":"Promoter hypermethylation influences the suppressive role of maternally expressed 3, a long non-coding RNA, in the development of epithelial ovarian cancer","volume":"32","author":"Sheng","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gokulnath, P., de Cristofaro, T., Manipur, I., Di Palma, T., Soriano, A.A., Guarracino, M.R., and Zannini, M. (2020). Long Non-Coding RNA HAND2-AS1 Acts as a Tumor Suppressor in High-Grade Serous Ovarian Carcinoma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114059"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"91009","DOI":"10.18632\/oncotarget.18857","article-title":"TXNDC5 is a cervical tumor susceptibility gene that stimulates cell migration, vasculogenic mimicry and angiogenesis by down-regulating SERPINF1 and TRAF1 expression","volume":"8","author":"Xu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3727\/096504016X14549667333963","article-title":"RNAi-Mediated Downregulation of FKBP14 Suppresses the Growth of Human Ovarian Cancer Cells","volume":"23","author":"Lu","year":"2016","journal-title":"Oncol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pronina, I.V., Uroshlev, L.A., Moskovtsev, A.A., Zaichenko, D.M., Filippova, E.A., Fridman, M.V., Burdennyy, A.M., Loginov, V.I., Kazubskaya, T.P., and Kushlinskii, N.E. (2022). Dysregulation of lncRNA-miRNA-mRNA Interactome as a Marker of Metastatic Process in Ovarian Cancer. Biomedicines, 10.","DOI":"10.3390\/biomedicines10040824"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.gene.2018.04.005","article-title":"Novel miRNA genes deregulated by aberrant methylation in ovarian carcinoma are involved in metastasis","volume":"662","author":"Loginov","year":"2018","journal-title":"Gene"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wang, X., Yung, M.M.H., Sharma, R., Chen, F., Poon, Y.T., Lam, W.Y., Li, B., Ngan, H.Y.S., Chan, K.K.L., and Chan, D.W. (2021). Epigenetic Silencing of miR-33b Promotes Peritoneal Metastases of Ovarian Cancer by Modulating the TAK1\/FASN\/CPT1A\/NF-kappaB Axis. Cancers, 13.","DOI":"10.3390\/cancers13194795"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.omtn.2019.11.003","article-title":"LncRNA MAGI2-AS3 Is Regulated by BRD4 and Promotes Gastric Cancer Progression via Maintaining ZEB1 Overexpression by Sponging miR-141\/200a","volume":"19","author":"Li","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_29","first-page":"1509","article-title":"Long non-coding RNA GAS5 inhibits tumorigenesis via miR-137 in melanoma","volume":"9","author":"Bian","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"762","DOI":"10.3892\/mmr.2021.12402","article-title":"Long non-coding RNA HAND2-AS1\/miR-106a\/PTEN axis re-sensitizes cisplatin-resistant ovarian cells to cisplatin treatment","volume":"24","author":"Li","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.canlet.2017.10.028","article-title":"Long non-coding RNA HAND2-AS1 inhibits invasion and metastasis in endometrioid endometrial carcinoma through inactivating neuromedin U","volume":"413","author":"Yang","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8589","DOI":"10.2147\/CMAR.S186002","article-title":"Epigenetic regulation of IncRNA KCNKI5-ASI in gastric cancer","volume":"11","author":"Zhang","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s00011-018-1186-z","article-title":"LncRNA MEG3 impacts proliferation, invasion, and migration of ovarian cancer cells through regulating PTEN","volume":"67","author":"Wang","year":"2018","journal-title":"Inflamm. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gokulnath, P., de Cristofaro, T., Manipur, I., Di Palma, T., Soriano, A.A., Guarracino, M.R., and Zannini, M. (2019). Long Non-Coding RNA MAGI2-AS3 is a New Player with a Tumor Suppressive Role in High Grade Serous Ovarian Carcinoma. Cancers, 11.","DOI":"10.3390\/cancers11122008"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6377","DOI":"10.1002\/cam4.3126","article-title":"MAGI2-AS3 suppresses MYC signaling to inhibit cell proliferation and migration in ovarian cancer through targeting miR-525-5p\/MXD1 axis","volume":"9","author":"Chang","year":"2020","journal-title":"Cancer Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s12935-020-01259-y","article-title":"LncRNA MEG3 suppressed the progression of ovarian cancer via sponging miR-30e-3p and regulating LAMA4 expression","volume":"20","author":"Liu","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e13204","DOI":"10.1016\/j.heliyon.2023.e13204","article-title":"MEG3 sponges miRNA-376a and YBX1 to regulate angiogenesis in ovarian cancer endothelial cells","volume":"9","author":"Li","year":"2023","journal-title":"Heliyon"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/s41419-022-05189-7","article-title":"LncRNA SEMA3B-AS1 inhibits breast cancer progression by targeting miR-3940\/KLLN axis","volume":"13","author":"Hu","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5475","DOI":"10.21873\/anticanres.16750","article-title":"lncRNA SEMA3B-AS1 Inhibits miR-513c-5p to Regulate the Progression of Triple-negative Breast Cancer","volume":"43","author":"Yu","year":"2023","journal-title":"Anticancer Res."},{"key":"ref_40","first-page":"5055684","article-title":"The lncRNA SEMA3B-AS1\/HMGB1\/FBXW7 Axis Mediates the Peritoneal Metastasis of Gastric Cancer by Regulating BGN Protein Ubiquitination","volume":"2022","author":"Huang","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13072-019-0283-8","article-title":"Aberrant methylation-mediated downregulation of lncRNA SSTR5-AS1 promotes progression and metastasis of laryngeal squamous cell carcinoma","volume":"12","author":"Wang","year":"2019","journal-title":"Epigenetics Chromatin"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s00404-020-05858-y","article-title":"Long noncoding RNA ZEB1-AS1 affects paclitaxel and cisplatin resistance by regulating MMP19 in epithelial ovarian cancer cells","volume":"303","author":"Dai","year":"2021","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11949","DOI":"10.1002\/jcb.28478","article-title":"lncRNA mortal obligate RNA transcript was downregulated in ovarian carcinoma and inhibits cancer cell proliferation by downregulating miRNA-21","volume":"120","author":"Chen","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Di Fiore, R., Suleiman, S., Drago-Ferrante, R., Felix, A., O\u2019Toole, S.A., O\u2019Leary, J.J., Ward, M.P., Beirne, J., Yordanov, A., and Vasileva-Slaveva, M. (2021). LncRNA MORT (ZNF667-AS1) in Cancer-Is There a Possible Role in Gynecological Malignancies?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157829"},{"key":"ref_45","first-page":"3199","article-title":"GAS5 is downregulated in gastric cancer cells by promoter hypermethylation and regulates adriamycin sensitivity","volume":"20","author":"Zhang","year":"2016","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"23571","DOI":"10.1002\/jcp.28926","article-title":"Upregulation of lncRNA GAS5 inhibits the growth and metastasis of cervical cancer cells","volume":"234","author":"Yang","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nrc2620","article-title":"Transitions between epithelial and mesenchymal states: Acquisition of malignant and stem cell traits","volume":"9","author":"Polyak","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41586-018-0040-3","article-title":"Identification of the tumour transition states occurring during EMT","volume":"556","author":"Pastushenko","year":"2018","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/jb\/mvy047","article-title":"Involvement of partial EMT in cancer progression","volume":"164","author":"Saitoh","year":"2018","journal-title":"J. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.tcb.2020.07.003","article-title":"EMT, MET, Plasticity, and Tumor Metastasis","volume":"30","author":"Bakir","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e108647","DOI":"10.15252\/embj.2021108647","article-title":"Dynamic EMT: A multi-tool for tumor progression","volume":"40","author":"Brabletz","year":"2021","journal-title":"EMBO J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e13423","DOI":"10.1111\/cpr.13423","article-title":"Heterogeneity and plasticity of epithelial-mesenchymal transition (EMT) in cancer metastasis: Focusing on partial EMT and regulatory mechanisms","volume":"56","author":"Li","year":"2023","journal-title":"Cell Prolif."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12943-023-01793-z","article-title":"EMT\/MET plasticity in cancer and Go-or-Grow decisions in quiescence: The two sides of the same coin?","volume":"22","author":"Akhmetkaliyev","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1074\/jbc.M116.750950","article-title":"MEG3 Long Noncoding RNA Contributes to the Epigenetic Regulation of Epithelial-Mesenchymal Transition in Lung Cancer Cell Lines","volume":"292","author":"Terashima","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1038\/s41467-017-01781-0","article-title":"Decoding critical long non-coding RNA in ovarian cancer epithelial-to-mesenchymal transition","volume":"8","author":"Mitra","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Zhang, L., Zhao, F., Li, W., Song, G., Kasim, V., and Wu, S. (2022). The Biological Roles and Molecular Mechanisms of Long Non-Coding RNA MEG3 in the Hallmarks of Cancer. Cancers, 14.","DOI":"10.3390\/cancers14246032"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/s41419-021-04401-4","article-title":"ALKBH5-mediated m(6)A demethylation of KCNK15-AS1 inhibits pancreatic cancer progression via regulating KCNK15 and PTEN\/AKT signaling","volume":"12","author":"He","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Meng, W., Cui, W., Zhao, L., Chi, W., Cao, H., and Wang, B. (2019). Aberrant methylation and downregulation of ZNF667-AS1 and ZNF667 promote the malignant progression of laryngeal squamous cell carcinoma. J. Biomed. Sci., 26.","DOI":"10.1186\/s12929-019-0506-0"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.7754\/Clin.Lab.2020.201129","article-title":"IncRNA ZNF667-AS1 Suppresses Epithelial Mesenchymal Transformation by Targeting TGF-beta1 in Oral Squamous Cell Carcinoma","volume":"67","author":"Zhao","year":"2021","journal-title":"Clin. Lab."},{"key":"ref_61","first-page":"155","article-title":"Long noncoding RNA MAGI2-AS3 inhibits bladder cancer progression through MAGI2\/PTEN\/epithelial-mesenchymal transition (EMT) axis","volume":"30","author":"Shen","year":"2021","journal-title":"Cancer Biomark. Sect. A Dis. Markers"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1080\/21655979.2021.2024653","article-title":"MicroRNA MiR-490-5p suppresses pancreatic cancer through regulating epithelial-mesenchymal transition via targeting MAGI2 antisense RNA 3","volume":"13","author":"Xu","year":"2022","journal-title":"Bioengineered"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"292","DOI":"10.2174\/156652410791065327","article-title":"The role of PEDF in tumor growth and metastasis","volume":"10","author":"Hoshina","year":"2010","journal-title":"Curr. Mol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/nrc3484","article-title":"The effects of PEDF on cancer biology: Mechanisms of action and therapeutic potential","volume":"13","author":"Becerra","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.3892\/ol.2017.5781","article-title":"Downregulation of FKBP14 by RNA interference inhibits the proliferation, adhesion and invasion of gastric cancer cells","volume":"13","author":"Wang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_66","first-page":"73","article-title":"Long non-coding RNA GAS5 inhibits ovarian cancer cell proliferation via the control of microRNA-21 and SPRY2 expression","volume":"16","author":"Ma","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"119","DOI":"10.21037\/atm-22-6394","article-title":"lncRNA GAS5 suppression of the malignant phenotype of ovarian cancer via the miR-23a-WT1 axis","volume":"11","author":"Zhou","year":"2023","journal-title":"Ann. Transl. Med."},{"key":"ref_68","first-page":"5968","article-title":"Silencing of KCNK15-AS1 inhibits lung cancer cell proliferation via upregulation of miR-202 and miR-370","volume":"18","author":"Peng","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1002\/1878-0261.12565","article-title":"Long noncoding RNA ZNF667-AS1 reduces tumor invasion and metastasis in cervical cancer by counteracting microRNA-93-3p-dependent PEG3 downregulation","volume":"13","author":"Li","year":"2019","journal-title":"Mol. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8895968","DOI":"10.1155\/2020\/8895968","article-title":"Analysis of Long Noncoding RNA ZNF667-AS1 as a Potential Biomarker for Diagnosis and Prognosis of Glioma Patients","volume":"2020","author":"Yuan","year":"2020","journal-title":"Dis. Markers"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s10585-019-09964-3","article-title":"Promoter hypermethylation-mediated downregulation of tumor suppressor gene SEMA3B and lncRNA SEMA3B-AS1 correlates with progression and prognosis of esophageal squamous cell carcinoma","volume":"36","author":"Dong","year":"2019","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5025868","DOI":"10.1155\/2023\/5025868","article-title":"lncRNA SSTR5-AS1 Predicts Poor Prognosis and Contributes to the Progression of Esophageal Cancer","volume":"2023","author":"Hu","year":"2023","journal-title":"Dis. Markers"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e35202","DOI":"10.1016\/j.heliyon.2024.e35202","article-title":"Prognostic significance of non-coding RNAs related to the tumorigenic epithelial-mesenchymal transition (EMT) process among ovarian cancer patients: A systematic review and meta-analysis","volume":"10","author":"Salimian","year":"2024","journal-title":"Heliyon"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"W556","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0022-2836(81)90087-5","article-title":"Identification of common molecular subsequences","volume":"147","author":"Smith","year":"1981","journal-title":"J. Mol. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects","volume":"310","year":"2013","journal-title":"JAMA"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Brierley, J.D., Gospodarowicz, M.K., and Wittekind, C. (2017). TNM Classification of Malignant Tumours, John Wiley & Sons. [8th ed.].","DOI":"10.1002\/9780471420194.tnmc26.pub3"},{"key":"ref_78","unstructured":"Kurman, R.J., Carcangiu, M.L., Herrington, C.S., and Young, R.H. (2014). WHO Classification of Tumours of Female Reproductive Organs, IARC Press. [4th ed.]."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.gene.2015.10.059","article-title":"Expression and DNA methylation alterations of seven cancer-associated 3p genes and their predicted regulator miRNAs (miR-129-2, miR-9-1) in breast and ovarian cancers","volume":"576","author":"Pronina","year":"2016","journal-title":"Gene"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Krasnov, G.S., Kudryavtseva, A.V., Snezhkina, A.V., Lakunina, V.A., Beniaminov, A.D., Melnikova, N.V., and Dmitriev, A.A. (2019). Pan-Cancer Analysis of TCGA Data Revealed Promising Reference Genes for qPCR Normalization. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00097"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gene.2016.12.018","article-title":"DNA methylation contributes to deregulation of 12 cancer-associated microRNAs and breast cancer progression","volume":"604","author":"Pronina","year":"2017","journal-title":"Gene"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nature03315","article-title":"Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs","volume":"433","author":"Lim","year":"2005","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Hendrickson, D.G., Hogan, D.J., Herschlag, D., Ferrell, J.E., and Brown, P.O. (2008). Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. 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