MicroRNA-214-3p targets the PLAGL2-MYH9 axis to suppress tumor proliferation and metastasis in human colorectal cancer

Aging (Albany NY). 2020 May 15;12(10):9633-9657. doi: 10.18632/aging.103233. Epub 2020 May 15.

Abstract

Evidence has shown that microRNAs (miRNAs) participate in the progression of CRC. Previous studies have indicated that miR-214-3p is abnormally expressed in various malignant tumors. However, the biological function it plays in CRC and the potential mechanism are unclear. Here, we demonstrated that miR-214-3p was obviously downregulated in CRC. Moreover, we found a strong correlation between the miR-214-3p level and tumor size and lymphatic metastasis. Furthermore, when miR-214-3p was decreased by an Lv-miR-214-3p inhibitor, the proliferation and migration of SW480 and HCT116 cells were significantly increased. As expected, the ability of proliferation and migration was significantly suppressed when miR-214-3p was overexpressed in DLD1 cells. According to the dual-luciferase reporter results, PLAGL2 was found to be a direct downstream molecule of miR-214-3p. Chromatin immunoprecipitation (CHIP) confirmed that MYH9, a well-known cytoskeleton molecule in CRC, was a direct targeting gene of PLAGL2. Silencing PLAGL2 or MYH9 could reverse the effect of a miR-214-3p inhibitor on CRC cells. In summary, our studies proved that low expression of miR-214-3p and overexpression of downstream PLAGL2 in CRC indicated a poor prognosis. MiR-214-3p suppressed the malignant behaviors of colorectal cancer by regulating the PLAGL2/MYH9 axis. MiR-214-3p might be a novel therapeutic target or prognostic marker for CRC.

Keywords: PLAGL2; colorectal cancer; metastasis; miR-214-3p; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • DNA-Binding Proteins / metabolism*
  • Female
  • HCT116 Cells
  • Humans
  • Male
  • MicroRNAs / physiology*
  • Middle Aged
  • Myosin Heavy Chains / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • MIRN214 microRNA, human
  • MYH9 protein, human
  • MicroRNAs
  • PLAGL2 protein, human
  • RNA-Binding Proteins
  • Transcription Factors
  • Myosin Heavy Chains