FNDC3B 3'-UTR shortening escapes from microRNA-mediated gene repression and promotes nasopharyngeal carcinoma progression.

Abstract

Alternative polyadenylation (APA), which induces shortening of the 3′‐UTR, is emerging as an important feature in cancer development and progression. Nevertheless, the effects and mechanisms of APA‐induced 3′‐UTR shortening in nasopharyngeal carcinoma (NPC) remain largely unclear. Fibronectin type III domain containing 3B (FNDC3B) tended to use proximal polyadenylation site and produce shorter 3′‐UTR according to our previous sequencing study. Herein, we found that FNDC3B with shorter 3′‐UTR could escape from miRNA‐mediated gene repression, and caused its increased expression in NPC. Knocking down of FNDC3B inhibited NPC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Overexpression of FNDC3B, especially those with shorter 3′‐UTR, promoted NPC progression. Furthermore, the mechanism study revealed that FNDC3B could bind to and stabilize myosin heavy chain 9 (MYH9) to activate the Wnt/β‐catenin signaling pathway. In addition, MYH9 could reverse the inhibitory effects of FNDC3B knockdown in NPC. Altogether, our results suggested that the 3′‐UTR shortening of FNDC3B mRNA mediated its overexpression in NPC and promoted NPC progression by targeting MYH9. This newly identified FNDC3B‐MYH9‐Wnt/β‐catenin axis could represent potential targets for individualized treatment in NPC.