MiR-93-5p promotes gastric cancer-cell progression via inactivation of the Hippo signaling pathway

Gene. 2018 Jan 30:641:240-247. doi: 10.1016/j.gene.2017.09.071. Epub 2017 Oct 16.

Abstract

MiR-93-5p has been previously found to be associated with gastric cancer (GC) tumorigenesis; however, the current understanding of its function in this context remains largely incomplete. In the present study, we showed that miR-93-5p was upregulated in GC tissues. We also demonstrated that miR-93-5p overexpression promoted the proliferation, migration, invasion, and chemoresistance of SGC-7901 cells in vitro, and conversely, that endogenously silencing miR-93-5p expression induced the opposite effects in HGC-27 cells. Overexpression of miR-93-5p was found to inactivate the Hippo pathway, and furthermore, miR-93-5p knockdown activated Hippo signaling. MiR-93-5p upregulation was also shown to inhibit the expression of two well-characterized Hippo pathway regulators, protocadherin Fat 4 (FAT4), and large tumor suppressors 2 (LATS2), at both the mRNA and protein level. Additionally, the results of bioinformatics analyses and luciferase reporter assays indicated that miR-93-5p directly targets the 3'-UTR of FAT4 and LATS2. Taken together, these results demonstrate that miR-93-5p promotes GC-cell progression via the inactivation of the Hippo signaling pathway, and thus, represents a potential therapeutic target for the treatment of GC.

Keywords: Gastric cancer; Hippo; Yap; miR-93-5p.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Cadherins / genetics
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics
  • Hippo Signaling Pathway
  • Humans
  • MicroRNAs / genetics*
  • Protein Serine-Threonine Kinases / genetics*
  • RNA, Messenger / genetics
  • Signal Transduction / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Tumor Suppressor Proteins / genetics
  • Up-Regulation / genetics

Substances

  • 3' Untranslated Regions
  • Cadherins
  • FAT4 protein, human
  • MIRN93 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • LATS2 protein, human
  • Protein Serine-Threonine Kinases