NUDT21 knockdown inhibits proliferation and promotes apoptosis of pancreatic ductal adenocarcinoma through EIF2 signaling

Exp Cell Res. 2020 Oct 15;395(2):112182. doi: 10.1016/j.yexcr.2020.112182. Epub 2020 Jul 22.

Abstract

The NUDT family is thought to play an important role in cancer growth and progression. However, the clinicopathologic significance and potential role of nucleotide diphosphate-linked X-component motif 21, NM_007006 (NUDT21) in pancreatic ductal adenocarcinoma (PDAC) remains largely unknown. In this study, we observed that NUDT21 was frequently up-expressed in PDAC. Clinical data revealed that its level positively correlated with poor survival of patients with PDAC. We found that knockdown of NUDT21 significantly inhibited cell proliferation and promoted apoptosis both in vitro and in vivo. Screening by microarray analysis and verifying by Western blot, we found that the EIF2 signaling pathway represented the main molecular mechanism underlying the effects of NUDT21 knockdown in PANC-1 cells, and PKR, HSPA5, EIF4E and DDIT3 may be its target genes. Thus, our results revealed for the first time that NUDT21, a valuable marker of PDAC prognosis, promotes tumor proliferation, inhibits cells apoptosis and might represent a potential target for gene-based therapy.

Keywords: Apoptosis; EIF2 signaling; NUDT21; Pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Cleavage And Polyadenylation Specificity Factor / genetics*
  • Cleavage And Polyadenylation Specificity Factor / metabolism
  • Endoplasmic Reticulum Chaperone BiP
  • Eukaryotic Initiation Factor-2 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Pancreatic Neoplasms

Substances

  • Biomarkers, Tumor
  • Cleavage And Polyadenylation Specificity Factor
  • Endoplasmic Reticulum Chaperone BiP
  • Eukaryotic Initiation Factor-2
  • HSPA5 protein, human
  • Nudt21 protein, human