lncRNA USP2-AS1 promotes colon cancer progression by modulating Hippo/YAP1 signaling

Am J Transl Res. 2020 Sep 15;12(9):5670-5682. eCollection 2020.

Abstract

Dysregulation of Hippo signaling by long non-coding RNA (lncRNA) contributes to colon adenocarcinoma (COAD) progression, while the underlying mechanisms remain elusive. Our study shows that lncRNA USP2-AS1 is a Yes-associated protein 1 (YAP1) binding lncRNA, and inactivates Hippo signaling in COAD cells. Moreover, our data indicated that USP2-AS1 lowered the phosph-YAP (S127), elevated the total level of YAP1, and triggered the expression of downstream target genes in COAD cells. The loss- and gain-of function assays demonstrated that USP2-AS1 promotes cellular proliferation and metastasis of COAD cells. Clinically, the USP2-AS1 levels were significantly elevated in COAD tissues and were positively correlated with tumor grade, size, and TNM stage. Collectively, these findings demonstrated that USP2-AS1 modulates and regulates Hippo signaling in COAD and could be a valuable therapeutic target.

Keywords: Hippo signaling; USP2-AS1; cell proliferation; lncRNA; metastasis.