miR‑508‑3p suppresses the development of ovarian carcinoma by targeting CCNA2 and MMP7

Int J Oncol. 2020 Jul;57(1):264-276. doi: 10.3892/ijo.2020.5055. Epub 2020 Apr 27.

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.

Keywords: microRNA-508-3p; proliferation; metastasis; CCNA2; MMP7; ovarian carcinoma.

Publication types

  • Observational Study

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adult
  • Aged
  • Carcinogenesis / drug effects
  • Carcinogenesis / genetics
  • Carcinoma, Ovarian Epithelial / genetics*
  • Carcinoma, Ovarian Epithelial / mortality
  • Carcinoma, Ovarian Epithelial / pathology
  • Carcinoma, Ovarian Epithelial / therapy
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cyclin A2 / genetics*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Kaplan-Meier Estimate
  • Matrix Metalloproteinase 7 / genetics*
  • MicroRNAs / agonists
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / prevention & control
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy
  • Ovariectomy
  • Ovary / pathology
  • Ovary / surgery
  • Prognosis

Substances

  • 3' Untranslated Regions
  • CCNA2 protein, human
  • Cyclin A2
  • MIRN508 microRNA, human
  • MicroRNAs
  • MMP7 protein, human
  • Matrix Metalloproteinase 7