Long Noncoding RNA KCNMB2-AS1 Increases ROCK1 Expression by Sponging microRNA-374a-3p to Facilitate the Progression of Non-Small-Cell Lung Cancer.

Abstract

PurposeThe expression and roles of most long noncoding RNAs (lncRNAs) in non–small-cell lung cancer (NSCLC) remain poorly understood. Thus, this study investigated KCNMB2 antisense RNA 1 (KCNMB2-AS1) expression in NSCLC and determined the roles and mechanisms of KCNMB2-AS1 in regulating NSCLC progression.MethodsKCNMB2-AS1 expression in NSCLC tissues and cells was detected using reverse transcription-quantitative polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were evaluated using Cell Counting Kit-8, flow cytometry, Transwell migration, and Transwell invasion assays, respectively. In vivo tumor xenograft models were constructed to assess tumorigenicity. Bioinformatics predictions were performed to identify microRNAs targeting KCNMB2-AS1. Interactions between KCNMB2-AS1 and miR-374a-3p were analyzed using RNA immunoprecipitation, luciferase reporter, and rescue experiments.ResultsKCNMB2-AS1 levels were increased in NSCLC tissues and cells. KCNMB2-AS1 silencing hindered NSCLC cell proliferation, migration, and invasion and promoted apoptosis in vitro. Additionally, KCNMB2-AS1 knockdown decreased tumor growth in vivo. Mechanistically, KCNMB2-AS1 functioned as an endogenous miR-374a-3p sponge and increased ρ-associated coiled-coil–containing protein kinase 1 (ROCK1) expression. Furthermore, increased miR-374a-3p/ROCK1 output attenuated KCNMB2-AS1 silencing-induced inhibition of NSCLC progression.ConclusionThe KCNMB2-AS1/miR-374a-3p/ROCK1 pathway drives NSCLC progression, suggesting that this pathway can be targeted to reduce NSCLC progression.