LINC10536 Attenuates Lung Adenocarcinoma Proliferation and Metastasis

Background: LUAD is a devastating disease with poor patient prognosis. Long non-coding RNAs (lncRNAs) have been implicated to play a critical role in LUAD progression. Methods: Differentially expressed and methylated tumor suppressor lncRNAs were found using TCGA, GSE81089) and E-MTAB-6957 datasets. The potential biological functions of LINC10536 were examined by loss- and gain-of-function models. Potential downstream pathway was validated by quantitative real-time polymerase chain reaction (RT-qPCR). RNA immunoprecipitation (RIP) arrays were employed to validate the binding between LINC10536 and enhancer of zeste homologue 2 (EZH2). Chromatin immunoprecipitation (CHIP) assays were used to demonstrate CDKN1B and E-cadherin as direct targets of EZH2. Results: The landscape of methylation-mediated tumor suppressor lncRNAs for LUAD were identified in this study. Overexpression of LINC10536 suppressed cell proliferation, cell cycle, invasion, migration and EMT of LUAD cells, whereas knockdown of LINC10536 promoted proliferative and metastatic potential of lung cancer cells in vitro and in vivo. As a nuclear lncRNA LINC10536 knockdown enhanced the occupancy capacity of EZH2 and H3K27me3 at the promoter region of CDKN1B and E-cadherin utilizing CHIP-qPCR. EZH2 knockdown partially reverses the malignant phenotype mediated by shLINC10536 in vitro and in vivo. Moreover, DNA methyltransferase inhibitor 5-azacytosine significantly facilitated LINC10536 expression and its biological functions. Interpretation: Our finding suggests LINC10536 might be a promising target for cancer diagnosis and therapy in clinical practice. Fundings: This project is partially supported by the National Natural Science Foundation of China (81772474, 82072563 to LC and 81803023 to YX). Declaration of Interest: The authors declare that they have no conflict of interest.