Nudt21-mediated alternative polyadenylation of MZT1 3′UTR contributes to pancreatic cancer progression

Autor: Yu Zhou, Jiabin Yang, Leyi Huang, Chao Liu, Min Yu, Rufu Chen, Quanbo Zhou
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 2, Pp 108822- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.108822
Popis: Summary: Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism and is involved in many diseases, but its function and mechanism in regulating pancreatic cancer (PC) pathogenesis remain unclear. In this study, we found that the 3′ UTR shortening of MZT1 was the most prominent APA event in PC liver metastases. The short-3′UTR isoform exerted a stronger effect in promoting cell proliferation and migration both in vitro and in vivo. NUDT21, a core cleavage factor involved in APA, promoted the usage of proximal polyadenylation sites (PASs) on MZT1 mRNA by binding to the UGUA element located upstream of the proximal PAS. High percentage of distal polyA site usage index of MZT1 was significantly associated with a better prognosis. These findings demonstrate a crucial mechanism that NUDT21-mediated APA of MZT1 could promote the progression of PC. Our findings provided a better understanding of the connection between PC progression and APA machinery.
Databáze: Directory of Open Access Journals