MicroRNA-92a Promotes Cell Proliferation in Cervical Cancer via Inhibiting p21 Expression and Promoting Cell Cycle Progression

Oncol Res. 2017 Jan 2;25(1):137-145. doi: 10.3727/096504016X14732772150262.

Abstract

MicroRNA-92a (miR-92a) generally plays a promoting role in human cancers, but the underlying mechanism in cervical cancer remains unclear. Here we studied the expression and clinical significance of miR-92a in cervical cancer, as well as the regulatory mechanism in the proliferation of cervical cancer cells. Our data indicated that miR-92a was significantly upregulated in cervical cancer tissues compared to their matched adjacent nontumor tissues (ANTs), and the increased miR-92a levels were significantly associated with a higher grade, lymph node metastasis, and advanced clinical stage in cervical cancer. In vitro study revealed that inhibition of miR-92a led to a significant reduction in the proliferation of HeLa cells via induction of cell cycle arrest at the G1 stage. In contrast, overexpression of miR-92a markedly promoted the proliferation of HeLa cells by promoting cell cycle progression. Further investigation revealed that miR-92a has a negative effect on protein levels, but not the mRNA levels, of p21 in HeLa cells, suggesting that p21 is a direct target of miR-92a. Overexpression of p21 eliminated the promoting effects of miR-92a on the proliferation and cell cycle progression of HeLa cells. However, knockdown of p21 reversed the suppressive effects of miR-92a downregulation on HeLa cell proliferation and cell cycle progression. Moreover, p21 was significantly downregulated in cervical cancer tissues compared to ANTs, suggesting that the increased expression of miR-92a may contribute to the decreased expression of p21, which further promotes cervical cancer growth. In conclusion, our study demonstrates that miR-92a promotes the proliferation of cervical cancer cells via inhibiting p21 expression and promoting cell cycle progression, highlighting the clinical significance of miR-92a in cervical cancer.

MeSH terms

  • Adult
  • Aged
  • Cell Cycle / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • RNA Interference*
  • Tumor Burden
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • MIRN92 microRNA, human
  • MicroRNAs