LncRNA MALAT1 accelerates non-small cell lung cancer progression via regulating miR-185-5p/MDM4 axis.

Non-small cell lung cancer (NSCLC) is the commonest malignancy with high death rate around the world. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is greatly overexpressed in multifarious cancers, including NSCLC. However, the precise mechanism of MALAT1 in NSCLC tumorigenesis is blurry. This paper aims to investigate the theory of MALAT1 action in NSCLC progression. The levels of MALAT1, microRNA (miR)-185-5p, and mouse double minute 4 protein (MDM4) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell proliferation and apoptosis were, respectively, determined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and flow cytometry. Cell migratory and invasive abilities were inspected by transwell assay. The binding relationship between miR-185-5p and MALAT1 or MDM4 was confirmed by dual-luciferase reporter assay. The impacts of MALAT1 on tumor growth in vivo were measured by a xenograft experiment. We found MALAT1 and MDM4 were upregulated and MALAT1 positively regulated the MDM4 expression. MALAT1 and MDM4 deletion significantly hindered the proliferation, metastasis, and expedited the apoptosis of NSCLC cells. MDM4 overexpression partly overturned the influence of MALAT1 downregulation on cell development. Moreover, miR-185-5p, as a target of MALAT1, could directly target MDM4, and miR-185-5p upregulation exerted inhibitory effects on NSCLC cells. Besides, knockdown of MALAT1 inhibited tumor growth in vivo through miR-185-5p/MDM4 axis in NSCLC. Collectively, MALAT1 contributed to proliferation, migration, invasion, and impeded apoptosis by regulating the MDM4 expression mediated by miR-185-5p in NSCLC cells.