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

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...

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Bibliographic Details
Published in:Experimental cell research 2020-10, Vol.395 (2), p.112182-112182, Article 112182
Main Authors: Zheng, Yan-song, Chen, Ming-liu, Lei, Wen-di, Zhu, Shan-lan, You, Xiao-qing, Liu, Yingchun
Format: Article
Language:English
Subjects:
Apoptosis
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
EIF2 signaling
Endoplasmic Reticulum Chaperone BiP
Eukaryotic Initiation Factor-2 - metabolism
Gene Expression Regulation, Neoplastic
Humans
Male
NUDT21
Pancreatic cancer
Pancreatic Neoplasms
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Summary: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.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2020.112182