MiR-490-5p Suppresses Cell Proliferation and Invasion by Targeting BUB1 in Hepatocellular Carcinoma Cells

Pharmacology. 2017;100(5-6):269-282. doi: 10.1159/000477667. Epub 2017 Aug 16.

Abstract

Objective: To verify that miR-490-5p could influence hepatocellular carcinoma (HCC) cells' proliferation, invasion, cycle, and apoptosis by targeting BUB1.

Methods: Quantitative real time-PCR (QRT-PCR) was used to determine the miR-490-5p expression. Immunohistochemistry, qRT-PCR, and Western blot were employed to detect BUB1 and transforming growth factor-beta (TGFβ/Smad) signaling-related proteins expression in hepatic tissues and cells. The luciferase assay was used to confirm the targeting relationship between miR-490-5p and BUB1. The Cell Counting Kit-8, colony formation, Transwell invasion, scratch healing assays, and flow cytometry analysis were conducted to evaluate HCC cells proliferation, invasion, migration, and apoptosis alteration after transfection.

Results: In HCC tissues and cells, lower expression of miR-490-5p was detected, while BUB1 was overexpressed than controls. The upregulation of miR-490-5p inhibited BUB1 expression and the overexpression of miR-490-5p or the under-expression of BUB1 inhibited HCC cells proliferation, migration, invasion, and increased the apoptosis rate.

Conclusion: MiR-490-5p could regulate TGFβ/Smad signaling pathways by inhibiting BUB1, which could then inhibit HCC cells proliferation, invasion, and migration as well as decrease cell viability and increase apoptosis.

Keywords: BUB1; Hepatocellular carcinoma; Transforming growth factor-beta/Smad signaling pathways; miR-490-5p.

Publication types

  • Retracted Publication

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Down-Regulation / genetics
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics*
  • Protein Serine-Threonine Kinases / genetics*
  • Signal Transduction / genetics
  • Up-Regulation / genetics

Substances

  • MIRN490 microRNA, human
  • MicroRNAs
  • BUB1 protein, human
  • Protein Serine-Threonine Kinases