MicroRNA-367-3p overexpression represses the proliferation and invasion of cervical cancer cells through downregulation of SPAG5-mediated Wnt/β-catenin signalling

Clin Exp Pharmacol Physiol. 2020 Apr;47(4):687-695. doi: 10.1111/1440-1681.13222. Epub 2020 Jan 19.

Abstract

MicroRNA-367-3p (miR-367-3p) has been previously reported as a cancer-related miRNA that is dysregulated in various cancer types and functions either as an oncogenic or as tumour suppressive miRNA. However, whether miR-367-3p is dysregulated in cervical cancer and, further, whether it contributes to the development and progression of the disease remains unknown. Here, our results demonstrated that miR-367-3p expression was markedly decreased in both cervical cancer tissues and cell lines compared with corresponding controls. In vitro experiments revealed that miR-367-3p overexpression repressed the proliferation and invasion of cervical cancer cells. Notably, sperm-associated antigen 5 (SPAG5) was identified as a target gene of miR-367-3p. Moreover, decreased expression of miR-367-3p was correlated with high expression of SPAG5 in cervical cancer tissue specimens. SPAG5 inhibition or miR-367-3p overexpression significantly downregulated Wnt/β-catenin signalling in cervical cancer cells. However, the antitumour effect mediated by miR-367-3p overexpression was partially reversed by SPAG5 overexpression. Overall, these findings demonstrate that miR-367-3p overexpression restricts the proliferation and invasion of cervical cancer cells through targeting SPAG5 to downregulate Wnt/β-catenin signalling, suggesting a mechanism for the tumour suppressive function of miR-367-3p in cervical cancer. Our study highlights the involvement of miR-367-3p/SPAG5/Wnt/β-catenin signalling axis in regulating the malignant progression of cervical cancer.

Keywords: SPAG5; Wnt; cervical cancer; miR-367-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Uterine Cervical Neoplasms / pathology*
  • Wnt Signaling Pathway / genetics*

Substances

  • Cell Cycle Proteins
  • MIRN367 microRNA, human
  • MicroRNAs
  • SPAG5 protein, human