Long noncoding RNA MIAT promotes non-small cell lung cancer progression by sponging miR-149-5p and regulating FOXM1 expression

Abstract

Abstract Background Long non-coding RNAs (lncRNAs) are a class of endogenous non-coding RNAs of longer than 200 bp that play crucial roles in cancer biology. Here, we assessed the tumorigenic properties of a long noncoding RNA, MIAT, in non-small cell lung cancer (NSCLC). Methods Survival and clinicopathological analyses were done in a cohort of 80 patients with NSCLC. MIAT expression level were determined by real-time quantitative reverse transcriptase PCR (qRT-PCR). Dual luciferase reporter assays were employed to test the interaction between MIAT and miR-149-5p. Ectopic overexpression and shRNA-mediated knockdown of MIAT, CCK-8 and colony formation assays, Transwell migration and invasion in vitro, and in vivo tumorigenesis experiment were used to evaluate the function of MIAT. Results MIAT was significantly up-regulated in NSCLC tissues and cell lines, and was closely associated with advanced pathological stage and poor overall survival. Gain- and loss-of-function experiments in cell lines and mouse xenograft models showed that MIAT promoted the proliferation, migration, and invasion of NSCLC cells in vitro and accelerated tumor growth in vivo. Luciferase assay, western blotting, qRT-PCR, and rescue experiments showed that, mechanistically, MIAT could directly bind to miR-149-5p, and subsequently served as a sponge to increase the expression level of Forkhead box M1 (FOXM1). Conclusions Our study reveals that MIAT acts as an oncogene in NSCLC via a novel MIAT/miR-149/FOXM1 axis, thus providing potential biomarkers and therapeutic targets for the management of NSCLC.

Keywords

• Non-small cell lung cancer
• long noncoding RNA
• MIAT
• miR-149-5p
• FOXM1