Knockdown of DDX46 suppresses the proliferation and invasion of gastric cancer through inactivating Akt/GSK-3β/β-catenin pathway

Exp Cell Res. 2021 Feb 1;399(1):112448. doi: 10.1016/j.yexcr.2020.112448. Epub 2020 Dec 19.

Abstract

DEAD-box RNA helicase 46 (DDX46) has recently been identified as a candidate oncogene in several types of human malignancies. To date, the role of DDX46 in gastric cancer has not been determined. The purpose of the current study was to explore the role of DDX46 in gastric cancer and the potential mechanism. DDX46-silecing or overexpressing gastric cancer cell lines were established to validate the role of DDX46. Our results showed that the expression of DDX46 was significantly increased in gastric cancer tissues and cell lines. Knockdown of DDX46 suppressed the proliferation and invasion of gastric cancer cells. Whereas, DDX46 overexpression enhanced the cell proliferation and invasion of gastric cancer cells. Furthermore, knockdown of DDX46 markedly suppressed the tumor growth of xenografts. Research into the mechanism revealed that DDX46 depletion inhibited the Akt/GSK-3β/β-catenin signaling pathway in gastric cancer cells. Notably, activation of Akt or β-catenin overexpression reversed the DDX46 depletion-mediated anti-cancer effect. In conclusion, these findings indicated that DDX46 exerted an oncogenic role in gastric cancer via regulating the Akt/GSK-3β/β-catenin signaling pathway. Thus, DDX46 might be utilized as a therapeutic anti-cancer target.

Keywords: Akt/GSK-3β/β-catenin signaling pathway; Cell invasion; Cell proliferation; DDX46; Gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Animals
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • DEAD-box RNA Helicases / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering / pharmacology
  • Ribonucleoprotein, U2 Small Nuclear / genetics*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • RNA, Small Interfering
  • Ribonucleoprotein, U2 Small Nuclear
  • beta Catenin
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • DDX46 protein, human
  • DEAD-box RNA Helicases