Shortening of the KHDRBS1 3'UTR by alternative cleavage and polyadenylation alters miRNA-mediated regulation and promotes gastric cancer progression

Xin Yu; Weibiao Kang; Jiajia Zhang; Changyu Chen; Yi Liu

Shortening of the KHDRBS1 3'UTR by alternative cleavage and polyadenylation alters miRNA-mediated regulation and promotes gastric cancer progression

Am J Transl Res. 2022 Sep 15;14(9):6574-6585. eCollection 2022.

Authors

Xin Yu¹, Weibiao Kang¹, Jiajia Zhang¹, Changyu Chen¹, Yi Liu¹

Affiliation

¹ Department of General Surgery, The First Affiliated Hospital of Anhui Medical University 218 Jixi Avenue, Hefei 230022, Anhui, China.

PMID: 36247240
PMCID: PMC9556470

Abstract

The shortening of the 3' untranslated regions (3'UTRs) due to alternative polyadenylation (APA) has become an important characteristic of cancer. However, the function of APA-induced 3'UTR shortening in gastric cancer (GC) remains unclear. KHDRBS1 (sam68), as an RNA-binding protein (RBP), is significantly upregulated in GC. In this study, we found that the 3'UTR of KHDRBS1 is generally shortened in GC tissues compared to paracancer tissues. Moreover, KHDRBS1 mRNA with a shortened 3'UTR can escape the inhibitory effect of miRNAs, resulting in its increased expression in GC. Overexpression of KHDRBS1, especially KHDRBS1 with a shortened 3'UTR, promotes the growth and metastasis of GC in vivo and in vitro. In conclusion, the experimental results show that shortening of the KHDRBS1 mRNA 3'UTR can mediate the overexpression of KHDRBS1 in GC cells and promote the progression of GC.

Keywords: APA; KHDRBS1; gastric cancer; metastasis; proliferation.