FNDC3B 3′‐UTR shortening escapes from microRNA‐mediated gene repression and promotes nasopharyngeal carcinoma progression

• Published in: Cancer science Vol. 111; no. 6; pp. 1991 - 2003
• Main Authors: Li, Ying‐Qing, Chen, Yang, Xu, Ya‐Fei, He, Qing‐Mei, Yang, Xiao‐Jing, Li, Ying‐Qin, Hong, Xiao‐Hong, Huang, Sheng‐Yan, Tang, Ling‐Long, Liu, Na
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-06-2020; John Wiley and Sons Inc
• Subjects: alternative polyadenylation; Cancer; Catenin; Cell adhesion & migration; Cell growth; Cell migration; Cell proliferation; Fibronectin; FND3CB; Genes; Kinases; Mass spectrometry; Medical prognosis; Metastases; MicroRNAs; miRNA; mRNA; mRNA 3′‐UTR shortening; Myosin; Nasopharyngeal carcinoma; Original; Plasmids; Polyadenylation; proliferation and metastasis; Proteins; Scientific imaging; Signal transduction; Wnt protein; China; FND3CB; nasopharyngeal carcinoma; proliferation and metastasis; mRNA 3′-UTR shortening; alternative polyadenylation
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.14394

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.
FNDC3B tended to use proximal polyadenylation site and produced shorter 3′‐UTR. FNDC3B with shorter 3′‐UTR could escape from microRNA‐mediated gene repression, and caused its increased expression in nasopharyngeal carcinoma (NPC) and promoted NPC progression by targeting MYH9.