MiR‑508‑3p Suppresses the Development of Ovarian Carcinoma by Targeting CCNA2 and MMP7

Overview

Journal Int J Oncol

Specialty Oncology

Date 2020 May 8

PMID 32377701

Citations 12

Authors

Fei Guo

Kai Zhang

Meiyue Li

Lei Cui

Guoyan Liu

Ye Yan

Wenyan Tian

Fei Teng

Yanfang Zhang

Chao Gao

Jinping Gao

Yingmei Wang

Fengxia Xue

Affiliations

Soon will be listed here.

Abstract

Ovarian cancer is the most lethal gynecological tumor, and the 5‑year survival rate is only ~40%. The poor survival rate is due to cancer diagnosis at an advanced stage, when the tumor has metastasized. A better understanding of the molecular pathogenesis of tumor growth and metastasis is needed to improve patient prognosis. MicroRNAs (miRs) regulate carcinogenesis and development of cancers. However, the role of miR‑508‑3p in ovarian cancer remains largely unknown. Thus, the present study aimed to investigate the possible functions of miR‑508‑3p in the modulation of development of ovarian cancer. The results of the present study demonstrated that miR‑508‑3p mimics inhibited ovarian cancer cell proliferation, migration and invasion. Reporter gene assay results demonstrated that miR‑508‑3p suppressed cancer cell proliferation by directly targeting the 3'‑untranslated region (UTR) of cyclin A2 (CCNA2) and suppressed migration and invasion by directly targeting the 3'‑UTR of matrix metalloproteinase 7 (MMP7). In addition, high CCNA2 and MMP7 expression levels were associated with low miR‑508‑3p expression in ovarian cancer tissues. Furthermore, miR‑508‑3p and CCNA2 were independent predictors for overall survival in patients with ovarian cancer. To the best of our knowledge, this is the first study to demonstrated that miR‑508‑3p suppressed ovarian cancer development by directly targeting CCNA2 and MMP7. The results of this study suggested the potential value of miR‑508‑3p and CCNA2 as prognostic indicators and therapeutics for ovarian cancer.

Citing Articles

Comprehensive analysis pinpoints CCNA2 as a prognostic and immunological biomarker in non-small cell lung cancer.

Zhang L, Wang S, Wang L BMC Pulm Med. 2025; 25(1):14.

PMID: 39799294 PMC: 11725219. DOI: 10.1186/s12890-025-03490-7.

A new method for network bioinformatics identifies novel drug targets for mucinous ovarian carcinoma.

Craig O, Lee S, Pilcher C, Saoud R, Abdirahman S, Salazar C NAR Genom Bioinform. 2024; 6(3):lqae096.

PMID: 39184376 PMC: 11344246. DOI: 10.1093/nargab/lqae096.

SETD7 Promotes Cell Proliferation and Migration via Methylation-mediated TAF7 in Clear Cell Renal Cell Carcinoma.

Zhang J, Duan B, Li F, Jing X, Li R, Cai S Int J Biol Sci. 2024; 20(8):3008-3027.

PMID: 38904013 PMC: 11186372. DOI: 10.7150/ijbs.93201.

MicroRNAs, long non-coding RNAs, and circular RNAs and gynecological cancers: focus on metastasis.

Rezaee A, Ahmadpour S, Jafari A, Aghili S, Tamehri Zadeh S, Rajabi A Front Oncol. 2023; 13:1215194.

PMID: 37854681 PMC: 10580988. DOI: 10.3389/fonc.2023.1215194.

Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens.

Schossig P, Coskun E, Arsenic R, Horst D, Sehouli J, Bergmann E Int J Mol Sci. 2023; 24(3).

PMID: 36768616 PMC: 9916968. DOI: 10.3390/ijms24032292.

References

Cooper W, Kohonen-Corish M, McCaughan B, Kennedy C, Sutherland R, Lee C . Expression and prognostic significance of cyclin B1 and cyclin A in non-small cell lung cancer. Histopathology. 2009; 55(1):28-36. DOI: 10.1111/j.1365-2559.2009.03331.x. View

Das E, Jana N, Bhattacharyya N . MicroRNA-124 targets CCNA2 and regulates cell cycle in STHdh(Q111)/Hdh(Q111) cells. Biochem Biophys Res Commun. 2013; 437(2):217-24. DOI: 10.1016/j.bbrc.2013.06.041. View

Zhang Q, Liu S, Parajuli K, Zhang W, Zhang K, Mo Z . Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition. Oncogene. 2016; 36(5):687-699. PMC: 5213194. DOI: 10.1038/onc.2016.240. View

Rojas V, Hirshfield K, Ganesan S, Rodriguez-Rodriguez L . Molecular Characterization of Epithelial Ovarian Cancer: Implications for Diagnosis and Treatment. Int J Mol Sci. 2016; 17(12). PMC: 5187913. DOI: 10.3390/ijms17122113. View

Gopinathan L, Tan S, Padmakumar V, Coppola V, Tessarollo L, Kaldis P . Loss of Cdk2 and cyclin A2 impairs cell proliferation and tumorigenesis. Cancer Res. 2014; 74(14):3870-9. PMC: 4102624. DOI: 10.1158/0008-5472.CAN-13-3440. View

Niedworok C, Tschirdewahn S, Reis H, Lehmann N, Szucs M, Nyirady P . Serum Chromogranin A as a Complementary Marker for the Prediction of Prostate Cancer-Specific Survival. Pathol Oncol Res. 2016; 23(3):643-650. DOI: 10.1007/s12253-016-0171-5. View

Liu G, Sun Y, Ji P, Li X, Cogdell D, Yang D . MiR-506 suppresses proliferation and induces senescence by directly targeting the CDK4/6-FOXM1 axis in ovarian cancer. J Pathol. 2014; 233(3):308-18. PMC: 4144705. DOI: 10.1002/path.4348. View

Parker B, Annala M, Cogdell D, Granberg K, Sun Y, Ji P . The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma. J Clin Invest. 2013; 123(2):855-65. PMC: 3561838. DOI: 10.1172/JCI67144. View

Yu X, Zhang X, Bi T, Ding Y, Zhao J, Wang C . MiRNA expression signature for potentially predicting the prognosis of ovarian serous carcinoma. Tumour Biol. 2013; 34(6):3501-8. DOI: 10.1007/s13277-013-0928-3. View

10.

Zhu R, Tian Y . Astrocyte elevated gene-1 increases invasiveness of NSCLC through up-regulating MMP7. Cell Physiol Biochem. 2015; 37(3):1187-95. DOI: 10.1159/000430242. View

11.

Yang D, Sun Y, Hu L, Zheng H, Ji P, Pecot C . Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer. Cancer Cell. 2013; 23(2):186-99. PMC: 3603369. DOI: 10.1016/j.ccr.2012.12.020. View

12.

Nozoe T, Inutsuka S, Honda M, Ezaki T, Korenaga D . Clinicopathologic significance of cyclin A expression in colorectal carcinoma. J Exp Clin Cancer Res. 2004; 23(1):127-33. View

13.

Sun Y, Hu L, Zheng H, Bagnoli M, Guo Y, Rupaimoole R . MiR-506 inhibits multiple targets in the epithelial-to-mesenchymal transition network and is associated with good prognosis in epithelial ovarian cancer. J Pathol. 2014; 235(1):25-36. PMC: 4268369. DOI: 10.1002/path.4443. View

14.

Li H, Ji J, Hou K, Lei Y, Zhao H, Wang J . Prediction of recurrence risk in early breast cancer using human epidermal growth factor 2 and cyclin A2. Chin Med J (Engl). 2010; 123(4):431-7. View

15.

Yamamoto S, Tsuda H, Miyai K, Takano M, Tamai S, Matsubara O . Cumulative alterations of p27-related cell-cycle regulators in the development of endometriosis-associated ovarian clear cell adenocarcinoma. Histopathology. 2010; 56(6):740-9. DOI: 10.1111/j.1365-2559.2010.03551.x. View

16.

Zhao L, Wang W, Xu L, Yi T, Zhao X, Wei Y . Integrative network biology analysis identifies miR-508-3p as the determinant for the mesenchymal identity and a strong prognostic biomarker of ovarian cancer. Oncogene. 2018; 38(13):2305-2319. PMC: 6755993. DOI: 10.1038/s41388-018-0577-5. View

17.

Maurel J, Nadal C, Garcia-Albeniz X, Gallego R, Carcereny E, Almendro V . Serum matrix metalloproteinase 7 levels identifies poor prognosis advanced colorectal cancer patients. Int J Cancer. 2007; 121(5):1066-71. DOI: 10.1002/ijc.22799. View

18.

Lee Y, Heo J, Kim T, Kang H, Kim G, Kim J . Significance of cell cycle regulatory proteins as malignant and prognostic biomarkers in ovarian epithelial tumors. Int J Gynecol Pathol. 2011; 30(3):205-17. DOI: 10.1097/PGP.0b013e3182063e71. View

19.

Sun Y, Guo F, Bagnoli M, Xue F, Sun B, Shmulevich I . Key nodes of a microRNA network associated with the integrated mesenchymal subtype of high-grade serous ovarian cancer. Chin J Cancer. 2015; 34(1):28-40. PMC: 4302087. DOI: 10.5732/cjc.014.10284. View

20.

Cribier A, Descours B, Chaves Valadao A, Laguette N, Benkirane M . Phosphorylation of SAMHD1 by cyclin A2/CDK1 regulates its restriction activity toward HIV-1. Cell Rep. 2013; 3(4):1036-43. DOI: 10.1016/j.celrep.2013.03.017. View