LINC00511 promotes the progression of non-small cell lung cancer through downregulating LATS2 and KLF2 by binding to EZH2 and LSD1.

Abstract

Lung cancer is a malignant tumor with extremely high morbidity and mortality. Recent studies have identified the vital role of LINC00511 (lncRNAs) in the development and progression of non-small cell lung cancer (NSCLC). In this research, we aim to explore the biological function of LINC00511 in the development and metastasis of NSCLC. LINC00511 expression in 57 paired NSCLC patients' tissues and matched normal tissues were detected by Real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation assay, colony formation assay and transwell assay were conducted to observe the biological behavior changes of NSCLC cells through the influence of LINC00511. In addition, dual-luciferase reporter gene assay, RNA immunoprecipitation assay (RIP) and, chromatin immunoprecipitation (ChIP) were performed to discover the potential targets of LINC00511 in NSCLC cells. LINC00511 was highly expressed in NSCLC tissues and cell lines compared with controls. LINC00511 expression was positively correlated with tumor size, tumor stage, lymph node metastasis and distant metastasis, but negatively correlated with overall survival (OS) of NSCLC patients. Receiver Operating Characteristic (ROC) curves suggested that LINC00511 could be an effective indicator to distinguish NSCLC patients from normal people. Cell counting kit-8 (CCK-8), flow cytometry and transwell assay showed that knockdown of LINC00511 in A549 cells decreased viability, accelerated apoptosis and inhibited invasive and migratory abilities. Overexpression of LINC00511 in PC9 cells obtained the opposite biological effects. Chromatin fractionation predicted that LINC00511 was mainly distributed in the nucleus. RIP and ChIP assay showed that LINC00551 directly bound to lysine-specific demethylase 1 (LSD1) and enhancer of zeste homolog 2 (EZH2). It inhibited expressions of LATS2 and KLF2 by binding to their promoter regions. LINC00511 is upregulated in NSCLC tissues and cell lines. It is closely related to tumor size, tumor stage, lymph node metastasis and, distant metastasis of NSCLC patients. Knockdown of LINC00511 attenuates proliferative, migratory and invasive capacities, but induces apoptosis of NSCLC cells. LATS2 and KLF2 are target genes of LINC00511, which are regulated by LINC00511 through binding to EZH2 and LSD1, thus influencing the progression of NSCLC.