A Novel Role for MiR-520a-3p in Regulating EGFR Expression in Colorectal Cancer

Cell Physiol Biochem. 2017;42(4):1559-1574. doi: 10.1159/000479397. Epub 2017 Jul 24.

Abstract

Background/aims: MicroRNAs (miRNAs) have been consistently demonstrated to be involved in colorectal cancer as either tumour oncogenes or tumour suppressors. However, the detailed role of miR-520a-3p in colorectal cancer remains poorly understood.

Methods: Quantitative RT-PCR and western blotting assays were used to measure miR-520a-3p and EGFR expression levels in colorectal cancer tissues, respectively. Luciferase reporter assay was employed to validate the direct targeting of EGFR by miR-520a-3p. Cell migration, apoptosis and cell cycle assays were performed to analyse the biological functions of miR-520a-3p and EGFR in colorectal cancer cells. In vivo experiment was performed to analyse the effects of miR-520a-3p and EGFR on the growth of colorectal cancer xenografts in mice.

Results: In this study, we found that miR-520a-3p was most likely to target the EGFR 3'-UTR, which was experimentally validated. In addition, we investigated the biological effects of EGFR inhibition by miR-520a-3p both in vitro and In vivo and found that miR-520a-3p could suppress cell migration, promote apoptosis, lead to colorectal cancer cell cycle arrest at the G0/G1 phase, and decelerate tumour growth in xenograft mice, potentially by targeting EGFR.

Conclusions: This study highlights a tumour suppressor role for miR-520a-3p in colorectal cancer via the regulation of EGFR expression. Thus, miR-520a-3p may be a novel molecular therapeutic target for colorectal cancer.

Keywords: Colorectal cancer; EGFR; MiR-520a-3p; MicroRNA.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Apoptosis / genetics
  • Base Sequence
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HT29 Cells
  • Heterografts
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Transplantation
  • Signal Transduction

Substances

  • MIRN520 microRNA, human
  • MicroRNAs
  • EGFR protein, human
  • ErbB Receptors