MiR-495 inhibits esophageal squamous cell carcinoma progression by targeting Akt1

Oncotarget. 2016 Aug 9;7(32):51223-51236. doi: 10.18632/oncotarget.9981.

Abstract

MicroRNAs are involved in tumor initiation and progression by regulating oncogenes and tumor suppressor genes. Here we found that miR-495 are lower in clinical ESCC tissues than in adjacent non-tumor tissues. Moreover, the lower miR-495 expression correlated with increased lymph node metastasis (LNM), invasion and TNM stage. miR-495 overexpression predicted a favorable outcome in ESCC patients. miR-495 targeted a site in the 3'-UTR of Akt1, and miR-495 levels correlated inversely with Akt1 protein levels in ESCC tissue samples. Overexpression of miR-495 suppressed cell proliferation, blocked G1/S phase transition, and decreased migration and invasion by two ESCC cell lines in vitro and in vivo. Restoration of Akt1 protein levels in miR-495-overexpressing ESCC cells attenuated the inhibitory effects of miR-495. In addition, miR-495 suppressed cell cycle transition and the EMT signaling pathway through targeting Akt1, thereby inhibiting ESCC cell proliferation, migration, and invasion. Our results suggest that miR-495 may act as a tumor suppressor by targeting Akt1 in ESCC.

Keywords: Akt1; esophageal squamous cell carcinoma; miR-495; progression.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Disease Progression
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / physiology*
  • Middle Aged
  • Proto-Oncogene Proteins c-akt / genetics*

Substances

  • MIRN495 microRNA, human
  • MicroRNAs
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt