Anti-tumor Role of MicroRNA-4782-3p in Epithelial Ovarian Cancer
Ovarian cancer ranks fifth in cancer death among women. The 5-year relative survival of all stages ovarian cancer is 47%. Identification of new molecular targets is required for the development of targeted therapy. MicroRNA (miRNA) are small, highly conserved RNA molecules involved in the regulation of gene expression. miR-4782-3p has shown tumor-suppressive activities in non-small cell lung cancer. Thus, it is possible that miR-4782-3p may play a role in the development of ovarian cancer. Herein, we analyzed the levels of miR-4782-3p in ovarian cancer tissue and cell lines and tested the function of miR-4782-3p in cell proliferation and cell apoptosis. We found that miR-4782-3p plays an inhibitory role in ovarian cancer growth. The data showed that ovarian cancer tissue and cell lines showed lower levels of miR-4782-3p, which inhibited cell growth and increased cell apoptosis. Moreover, PDGFRα was identified as a direct target of miR-4782-3p. In conclusion, our data indicated that miR-4782-3p has an inhibitory impact on ovarian cancer.
Reid BM, Permuth JB, Sellers TA, 2017, Epidemiology of Ovarian Cancer: A Review. Cancer Biol Med, 14:9–32.
Holschneider CH, Berek JS, editors, 2000, Ovarian Cancer: Epidemiology, Biology, and Prognostic Factors. In: Seminars in Surgical Oncology. Hoboken, New Jersey: Wiley Online Library.
Permuth-Wey J, Sellers TA, 2009, Epidemiology of Ovarian Cancer. In: Cancer Epidemiology. Berlin: Springer, pp.413–37. DOI: 10.1007/978-1-60327-492-0_20.
Nagle CM, 2011, Ovarian Cancer Epidemiology. In: Encyclopedia of Cancer: Berlin: Springer, pp.2686–9.
Lacey JV Jr., Mink PJ, Lubin JH, et al., 2002, Menopausal Hormone Replacement Therapy and Risk of Ovarian Cancer. JAMA, 288:334–41. DOI: 10.1001/jama.288.3.334.
Greene MH, Clark JW, Blayney DW, editors, 1984, The Epidemiology of Ovarian Cancer. In: Seminars in Oncology. Amsterdam, Netherlands: Elsevier.
Momenimovahed Z, Tiznobaik A, Taheri S, et al., 2019, Ovarian Cancer in the World: Epidemiology and Risk Factors. Int J Womens Health, 11:287. DOI: 10.2147/ijwh.s197604.
Yap TA, Carden CP, Kaye SB, 2009, Beyond Chemotherapy: Targeted Therapies in Ovarian Cancer. Nat Rev Cancer, 9:167. DOI: 10.1038/nrc2583.
Bartel DP, 2009, MicroRNAs: Target Recognition and Regulatory Functions. Cell, 136:215–33. DOI: 10.1016/j.cell.2009.01.002.
Cortez MA, Anfossi S, Ramapriyan R, et al., 2019, Role of miRNAs in Immune Responses and Immunotherapy in Cancer. Genes Chromosomes Cancer, 58:244–53. DOI: 10.1002/gcc.22725.
Hu W, Tan C, He Y, et al., 2018, Functional miRNAs in Breast Cancer Drug Resistance. Oncol Ther, 11:1529–41.
O’Bryan S, Dong S, Mathis JM, et al., 2017, The Roles of Oncogenic miRNAs and their Therapeutic Importance in Breast Cancer. Eur J Cancer, 72:1–11. DOI: 10.1016/j.ejca.2016.11.004.
Slattery ML, Mullany LE, Sakoda LC, et al., 2018, Dysregulated Genes and miRNAs in the Apoptosis Pathway in Colorectal Cancer Patients. Apoptosis, 23:237–50. DOI: 10.1007/s10495-018-1451-1.
Yang F, Ning Z, Ma L, et al., 2017, Exosomal miRNAs and miRNA Dysregulation in Cancer-associated Fibroblasts. Mol Cancer, 16:1–10. DOI: 10.1186/s12943-017-0718-4.
Hirschberger S, Hinske LC, Kreth S, 2018, MiRNAs: Dynamic Regulators of Immune Cell Functions in Inflammation and Cancer. Cancer Lett, 431:11–21. DOI: 10.1016/j.canlet.2018.05.020.
Florczuk M, Szpechcinski A, Chorostowska-Wynimko J, 2017, miRNAs as Biomarkers and Therapeutic Targets in Non-small Cell Lung Cancer: Current Perspectives. Target Oncol, 12:179–200. DOI: 10.1007/s11523-017-0478-5.
Taylor DD, Gercel-Taylor C, 2008, MicroRNA Signatures of Tumor-derived Exosomes as Diagnostic Biomarkers of Ovarian Cancer. Gynecol Oncol, 110:13–21. DOI: 10.1016/j.ygyno.2008.04.033.
Bo W, Hu Y, Feng X, et al., 2016, The Tumor Suppressor Role of miR-4782-3p in Hepatocellular Carcinoma. Oncol Rep, 35:2107–12. DOI: 10.3892/or.2016.4568.
Wu N, Zhang C, Bai C, et al., 2014, MiR-4782-3p Inhibited Non-small Cell Lung Cancer Growth via USP14. Cell Physiol Biochem, 33:457–67. DOI: 10.1159/000358626.
Ding H, Wu X, Boström H, et al., 2004, A Specific Requirement for PDGF-C in Palate Formation and PDGFR-a Signaling. Nat Genet, 36:1111. DOI: 10.1038/ng1415.
Yi C, Li L, Chen K, et al., 2012, Expression of c-Kit and PDGFRalpha in Epithelial Ovarian Tumors and Tumor Stroma. Oncol Lett, 3:369–72.
Matei D, Emerson R, Lai Y, et al., 2006, Autocrine Activation of PDGFRa Promotes the Progression of Ovarian Cancer. Oncogene, 25:2060. DOI: 10.1038/sj.onc.1209232.
Peng Y, Guo JJ, Liu YM, et al., 2014, MicroRNA-34A Inhibits the Growth, Invasion and Metastasis of Gastric Cancer by Targeting PDGFR and MET Expression. Biosci Rep, 34:e00112. DOI: 10.1042/bsr20140020.
Xiong GB, Zhang GN, Xiao Y, et al., 2015, MicroRNA-219-5p Functions as a Tumor Suppressor Partially by Targeting Platelet-derived Growth Factor Receptor Alpha in Colorectal Cancer. Neoplasma, 62:855–63. DOI: 10.4149/neo_2015_104.
Li D, Liu X, Lin L, et al., 2011, MicroRNA-99a Inhibits Hepatocellular Carcinoma Growth and Correlates with Prognosis of Patients with Hepatocellular Carcinoma. J Biol Chem, 286:36677–85. DOI: 10.1074/jbc.m111.270561.
Song B, Zhang C, Li G, et al., MiR-940 Inhibited Pancreatic Ductal Adenocarcinoma Growth by Targeting MyD88. Cell Physiol Biochem, 35:1167–77. DOI: 10.1159/000373941.
Zhou Q, Yu Y, 2015, Upregulated CDK16 Expression in Serous Epithelial Ovarian Cancer Cells. Med Sci Monit, 21:3409–14. DOI: 10.12659/msm.894990.
Li H, Xu Y, Qiu W, et al., 2015, Tissue miR-193b as a Novel Biomarker for Patients with Ovarian Cancer. Med Sci Monit, 21:3929. DOI: 10.12659/msm.895407.
Mosmann T, 1983, Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays. J Immunol Methods, 65:55–63. DOI: 10.1016/0022-1759(83)90303-4.
Agarwal V, Bell GW, Nam JW, et al., 2015, Predicting Effective microRNA Target Sites in Mammalian mRNAs. Elife, 4:e05005. DOI: 10.7554/elife.05005.
Heldin CH, Westermark B, 1999, Mechanism of Action and In Vivo Role of Platelet-derived Growth Factor. Physiol Rev, 79:1283–316. DOI: 10.1152/physrev.1999.79.4.1283.
Dabrow MB, Francesco MR, McBrearty FX, et al., 1998, The Effects of Platelet-derived Growth Factor and Receptor on Normal and Neoplastic Human Ovarian Surface Epithelium. Gynecol Oncol, 71:29–37. DOI: 10.1006/gyno.1998.5121.
Wang Y, Hu C, Dong R, et al., 2011, Platelet-derived Growth Factor-D Promotes Ovarian Cancer Invasion by Regulating Matrix Metalloproteinases 2 and 9. Asian Pac J Cancer Prev, 12:3367–70. DOI: 10.1016/j.ygyno.2003.12.041.
Henriksen R, Funa K, Wilander E, et al., 1993, Expression and Prognostic Significance of Platelet-derived Growth Factor and its Receptors in Epithelial Ovarian Neoplasms. Cancer Res, 53:4550–4.
Apte SM, Bucana CD, Killion JJ, et al., Expression of Platelet-derived Growth Factor and Activated Receptor in Clinical Specimens of Epithelial Ovarian Cancer and Ovarian Carcinoma Cell Lines. Gynecol Oncol, 93:78–86.
Luo H, Wang X, Ge H, et al., 2019, Inhibition of Ubiquitinspecific Protease 14 Promotes Connexin 32 Internalization and Counteracts Cisplatin Cytotoxicity in Human Ovarian Cancer Cells. Oncol Rep, 42:1237–47. DOI: 10.3892/or.2019.7232.
Han KH, Kwak M, Lee TH, et al., 2019, USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro. Int J Mol Sci, 20:5300.
Wang Y, Wang J, Zhong J, et al., 2015, Ubiquitin-specific Protease 14 (USP14) Regulates Cellular Proliferation and Apoptosis in Epithelial Ovarian Cancer. Med Oncol, 32:379. DOI: 10.1007/s12032-014-0379-8.
Alshamrani AA. Roles of microRNAs in Ovarian Cancer Tumorigenesis: Two Decades Later, What Have We Learned? Front Oncol, 10:1084. DOI: 10.3389/fonc.2020.01084.
Lee YS, Dutta A, 2007, The Tumor Suppressor MicroRNA let-7 Represses the HMGA2 Oncogene. Genes Dev, 21:1025–30. DOI: 10.1101/gad.1540407.
Mayr C, Hemann MT, Bartel DP, 2007, Disrupting the Pairing between let-7 and Hmga2 Enhances Oncogenic Transformation. Science, 315:1576–9. DOI: 10.1126/science.1137999.
Park SM, Shell S, Radjabi AR, et al., 2007, Let-7 Prevents Early Cancer Progression by Suppressing Expression of the Embryonic Gene HMGA2. Cell Cycle, 6:2585–90. DOI: 10.4161/cc.6.21.4845.
Liu G, Sun Y, Ji P, et al., 2014, MiR-506 Suppresses Proliferation and Induces Senescence by Directly Targeting the CDK4/6-FOXM1 Axis in Ovarian Cancer. J Pathol, 233:308–18. DOI: 10.1002/path.4348.
Xia B, Yang S, Liu T, et al., 2015, miR-211 Suppresses Epithelial Ovarian Cancer Proliferation and Cell-cycle Progression by Targeting Cyclin D1 and CDK6. Mol Cancer, 14:57. DOI: 10.1186/s12943-015-0322-4.
Li J, Shao W, Feng H, 2019, MiR-542-3p, a microRNA Targeting CDK14, Suppresses Cell Proliferation, Invasiveness, and Tumorigenesis of Epithelial Ovarian Cancer. Biomed Pharmacother, 110:850–6. DOI: 10.1016/j.biopha.2018.11.104.