MicroRNA-147b Promotes Proliferation and Invasion of Human Colorectal Cancer by Targeting RAS Oncogene Family (RAP2B)

Pathobiology. 2019;86(4):173-181. doi: 10.1159/000495253. Epub 2019 May 23.

Abstract

Background: MicroRNAs (miRNAs), a class of small-regulatory RNA molecules, were closely involved in the pathogenesis of a broad-spectrum of colorectal cancer (CRC). But role of miR-147b in CRC still remains unclear.

Methods: Real-time RT-PCR or Western blotting was utilized to detect the expressions of miR-147b and RAP2B in CRC cell lines and tissues. Luciferase reporter assays were conducted to detect the associations between miR-147b and 3'UTRs of RAP2B. A series of assays were performed to evaluate the effect of miR-147b on proliferation, migration, and invasion of CRC in vitro and in vivo.

Results: We found that the level of miR-147b was significantly lower in CRC tissues than in normal tissues (p = 0.0006). Enforced expression of miR-147b led to suppression of CRC cell proliferation in vitro and tumor growth in vivo. Specifically, miR-147b promoted proliferation by arresting CRC cells in the G1/G0 phase. Mechanically, RAP2B was identified as a direct target gene of miR-147b and RAP2B rescued the suppression of proliferation and invasion reduced by miR-147b in CRC cells.

Conclusions: miR-147b not only plays important roles in the regulation of cell proliferation and tumor growth in CRC, which might be a potential prognostic marker or therapeutic target for CRC.

Keywords: Colorectal cancer; Invasion; Proliferation; RAP2B; miR-147b.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness*
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / pathology
  • rap GTP-Binding Proteins / genetics*

Substances

  • MIRN147 microRNA, human
  • MicroRNAs
  • RAP2B protein, human
  • rap GTP-Binding Proteins