MicroRNA-542-3p suppresses cellular proliferation of bladder cancer cells through post-transcriptionally regulating survivin

Gene. 2016 Apr 1;579(2):146-52. doi: 10.1016/j.gene.2015.12.048. Epub 2015 Dec 23.

Abstract

Aim: To investigate the clinical significance of microRNA-542-3p (miR-542-3p) and its target gene survivin in human bladder cancer, and to determine their functions in malignant phenotypes of this disease.

Methods: Expression levels of miR-542-3p and survivin mRNA in bladder cancer and adjacent normal tissues were detected by quantitative RT-PCR. Cell proliferation and cell cycle were assessed by cell viability assay, flow cytometry and colony formation assay based on two human bladder cancer cell lines.

Results: MiR-542-3p expression was downregulated, while survivin mRNA expression was upregulated in bladder cancer tissues, compared to adjacent normal tissues (both P<0.001). Importantly, the expression level of miR-542-3p in bladder cancer tissues was negatively correlated with that of survivin mRNA. MiR-542-3p-low and/or survivin-high expression were all significantly associated with tumor stage (all P<0.05) and tumor recurrence (all P<0.05) of patients with bladder cancer. Moreover, the enforced expression of miR-542-3p remarkably inhibited cell proliferation by inducing G1 phase arrest in both T24 and J82 cells, and decreased the expression level of survivin protein. In contrast, the knock-down of miR-542-3p dramatically promoted the proliferation of bladder cancer cells by accelerating the progression of cell cycle and increased the expression level of survivin protein.

Conclusion: MiR-542-3p and its target gene survivin may play crucial roles in the aggressive progression of human bladder cancer. More interestingly, miR-542-3p may function as a tumor suppressor and inhibit the proliferation of bladder cancer cells, implying that miR-542-3p-survivin signal axis might be a novel therapeutic target of this disease.

Keywords: Bladder cancer; Cell proliferation; Clinicopathological characteristics; MicroRNA-542-3p; Survivin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inhibitor of Apoptosis Proteins / biosynthesis*
  • Inhibitor of Apoptosis Proteins / genetics
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • RNA, Messenger / biosynthesis*
  • Survivin
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • MIRN542 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Survivin