LncRNA MKLN1-AS promotes glioma tumorigenesis and growth via activating the Hippo pathway through miR-126-5p/TEAD1 axis.

Abstract

The involvement of long non-coding RNAs (lncRNAs) in glioma carcinogenesis has gradually been identified. Herein, we aimed to explore the function and mechanism of lncRNA muskelin 1 antisense RNA (MKLN1-AS) in glioma cell oncogenic properties. Quantitative real-time polymerase chain reaction was utilized to test the expression of MKLN1-AS, miR-126-5p, and TEAD1 (TEA Domain Transcription Factor 1) mRNA expression. Oncogenic properties of glioma cells were characterized using 5-ethynyl-2'-deoxyuridine, flow cytometry, wound healing, transwell, and tube formation assays, respectively. Levels of TEAD1 protein, mobility-related proteins, and Hippo pathway-related proteins were examined by Western blotting. The binding between miR-126-5p and MKLN1-AS or TEAD1 was confirmed by using dual-luciferase reporter and pull-down assays. The murine xenograft model was established for in vivo analysis. Levels of MKLN1-AS in glioma tissues and cell lines were higher, functionally, MKLN1-AS deficiency could suppress glioma cell proliferation, migration, invasion, and angiogenesis, and induce apoptosis in vitro, as well as impede tumor growth in vivo. Mechanistically, miR-126-5p was targeted by MKLN1-AS, miR-126-5p directly targeted TEAD1. The suppressing effects of MKLN1-AS deficiency on glioma cell oncogenic properties were abolished by TEAD1 overexpression or miR-126-5p inhibition. Besides, MKLN1-AS/miR-126-5p mediates the activation of Hippo pathway by TEAD1. MKLN1-AS knockdown weakened glioma cell oncogenic phenotypes and growth via TEAD1-Hippo pathway through miR-126-5p, indicating a new therapeutic target for glioma molecular therapy.