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

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. AJTR