LncRNA TRPM2-AS promotes cell proliferation, migration, and invasion by regulating the miR-195-5p/COP1 axis in bladder cancer

Abstract

Bladder cancer (BLCA) is one of the most frequent malignant tumors worldwide, with markedly poor prognosis when distant metastasis occurs. Long noncoding RNA (lncRNA) TRPM2-AS has been reported to play an oncogenic role in several cancers. Although TRPM2-AS was previously revealed to suppress BLCA cell growth, its role in BLCA cell metastasis remains largely unknown. In our study, TRPM2-AS, miR-195-5p, and COP1 relative expression in BLCA cells was estimated by RT-qPCR. Through MTT, EdU, colony formation, wound-healing, Transwell, and western blotting assays, the biological effects of TRPM2-AS and COP1 on BLCA cell proliferation, migration, invasion, and EMT were evaluated. Target association between miR-195-5p and TRPM2-AS (or COP1) was confirmed by RNA pull-down, RIP, and luciferase activity assays. The nucleocytoplasmic localization of TRPM2-AS in BLCA cells was measured by FISH assay. Xenograft mouse models of BLCA were used to validate the role of TRPM2-AS on tumor growth and EMT in vivo. Our results showed that TRPM2-AS and COP1 expression was increased, while miR-195-5p expression was decreased in BLCA cells and tissues. TRPM2-AS silencing repressed BLCA cell growth, migration, invasion, and EMT. TRPM2-AS acted as a competing endogenous RNA (ceRNA) to spongemiR-195-5p, thereby positively regulating COP1 expression and activating the PI3K/AKT signaling. Overexpressing COP1 antagonized the influence of TRPM2-AS knockdown on BLCA cell growth, migration, invasion, and EMT. Additionally, TRPM2-AS knockdown inhibited tumor growth, EMT, and the PI3K/AKT signaling, attenuated COP1 expression, and enhanced miR-195-5p expression in xenograftmouse models. Collectively, TRPM2-AS functions as an oncogene in BLCA development via the miR-195-5p/COP1 axis.

Keywords: Bladder cancer; COP1; MiR-195-5p; PI3K/AKT signaling pathway; TRPM2-AS.