DDX21 promotes gastric cancer proliferation by regulating cell cycle

Biochem Biophys Res Commun. 2018 Nov 10;505(4):1189-1194. doi: 10.1016/j.bbrc.2018.10.060. Epub 2018 Oct 12.

Abstract

DEAD (Asp-Glu-Ala-Asp) cassette helicase 21 (DDX21) is an ATP-dependent RNA helicase that is overexpressed in various malignancies. There is increasing evidence that DDX21 is involved in carcinogenesis and cancer progression by promoting cell proliferation. However, the functional role of DDX21 in gastric cancer is largely unknown. In this study, we observed that DDX21 was significantly up-regulated in gastric cancer tissues compared to paired adjacent normal tissues. The expression of DDX21 was closely related to the pathological stage of gastric cancer. In vitro and in vivo studies had shown that knockdown of DDX21 inhibited gastric cancer cell proliferation, colony formation, G1/S cell cycle transition and xenograft growth, while ectopic expression of DDX21 promoted these cell functions. Mechanically, DDX21 induced gastric cancer cell growth by up-regulating levels of Cyclin D1 and CDK2. Taken together, these results revealed a novel role for DDX21 in the proliferation of gastric cancer cells via the Cyclin D1 and CDK2 pathways. Therefore, DDX21 can be used as a therapeutic target for gastric cancer.

Keywords: CDK2; Cyclin D1; DEAD (Asp-Glu-Ala-Asp) box helicase 21 (DDX21); Gastric cancer; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis
  • Cell Cycle*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • DEAD-box RNA Helicases / physiology*
  • Female
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology

Substances

  • CCND1 protein, human
  • Cyclin D1
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • DDX21 protein, human
  • DEAD-box RNA Helicases