MicroRNA-374b reduces the proliferation and invasion of colon cancer cells by regulation of LRH-1/Wnt signaling

Gene. 2018 Feb 5:642:354-361. doi: 10.1016/j.gene.2017.11.019. Epub 2017 Nov 8.

Abstract

Deregulation of microRNA (miRNA) has been suggested as a critical event in colon cancer development and progression. Recent studies have suggested that miR-374b is a novel cancer-related miRNA involved in several cancer types. Thus far, very little is known about the role of miR-374b in colon cancer; therefore, the goal of this study was to investigate the potential role of miR-374b in colon cancer. Here, we showed that miR-374b expression was significantly downregulated in colon cancer tissues and cell lines. Overexpression of miR-374b inhibited the proliferation and invasion of colon cancer cells, while miR-374b suppression promoted colon cancer cell proliferation and invasion. Liver receptor homolog-1 (LRH-1) was identified as a target of miR-374b in colon cancer cells. Both the mRNA and protein expression of LRH-1 were regulated by miR-374b. In addition, an inverse correlation between LRH-1 mRNA and miR-374b expression was evidenced in colon cancer specimens. Notably, overexpression of miR-374b also downregulated the Wnt signaling in colon cancer cells. Furthermore, restoration of LRH-1 expression significantly abolished the antitumor effect of miR-374b in colon cancer cells. These findings suggest that miR-374b inhibits colon cancer cell proliferation and invasion through downregulation of LRH-1 expression. Inhibiting LRH-1 by miR-374b may represent a novel therapeutic strategy for the treatment of colon cancer.

Keywords: Colon cancer; LRH-1; Wnt; miR-374b.

MeSH terms

  • 3' Untranslated Regions
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / genetics*
  • Down-Regulation*
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Promoter Regions, Genetic
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Wnt Signaling Pathway

Substances

  • 3' Untranslated Regions
  • MIRN374 microRNA 374, human
  • MicroRNAs
  • NR5A2 protein, human
  • Receptors, Cytoplasmic and Nuclear