miR-223-RhoB signaling pathway regulates the proliferation and apoptosis of colon adenocarcinoma

Chem Biol Interact. 2018 Jun 1:289:9-14. doi: 10.1016/j.cbi.2018.04.016. Epub 2018 Apr 13.

Abstract

MicroRNAs (miRNAs) can function as tumor suppressor or oncogenic genes. The putative targets of miR-223 include tumor suppressor gene, RhoB. Here we sought to investigate the role of miR-223-RhoB signaling pathway in proliferation of colon cancer. We used Western blot, immunofluorescence staining, or RT-PCR to detect expression levels of miR-223 and RhoB in colon adenocarcinoma and adjacent non-cancerous tissue samples, or in human colon adenocarcinoma cell lines. MTT assay was used to determine proliferation and apoptosis in cell lines. We further used Western blot to determine levels of cell cycle regulators CDK1 and Cyclin B1 with anti-miR-223 or apoptosis with overexpression of RhoB. The expression level of miR-223 was significantly upregulated in clinical samples and cell lines of colon adenocarcinoma, in contrast to down-regulation of RhoB. In addition, we showed that inhibition of miR-223 led to upregulation of RhoB and in turn suppression of proliferation of colon adenocarcinoma. Moreover, inhibition of miR-223 or overexpression of RhoB induced cell arrest or apoptosis in colon adenocarcinoma. These results suggest that miR-223-RhoB signaling pathway plays an important role in modulation of proliferation, cell arrest, and apoptosis in colon cancer.

Keywords: Apoptosis; Colon cancer; Proliferation; RhoB; miR-223.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Apoptosis* / genetics
  • Base Sequence
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology*
  • Down-Regulation / genetics
  • Female
  • G2 Phase / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Mitosis / genetics
  • Signal Transduction*
  • Up-Regulation / genetics
  • rhoB GTP-Binding Protein / metabolism*

Substances

  • MIRN141 microRNA, human
  • MIRN223 microRNA, human
  • MicroRNAs
  • rhoB GTP-Binding Protein