LncRNA MATN1-AS1 prevents glioblastoma cell from proliferation and invasion via RELA regulation and MAPK signaling pathway

Abstract

Glioblastoma (GBM) is one of the most aggressive and malignant tumor types. Despite treatment advances, GBM pathogenesis still remains largely unknown. MATN1-AS1, an intron-retained long non-coding RNA (lncRNA), has been implicated in GBM development. However, the underlying mechanism has not been identified. This study aimed to examine MATN1-AS1 expression and uncover its role in GBM. LncRNAs with low expression levels were selected by analyzing brain glioma-related genes. The relative mRNA level of MATN1-AS1 was quantified using RT-qPCR in 75 GBM tumors and 10 normal brain tissues. Overall survival was assessed using the Kaplan-Meier method. RT-qPCR and immunoblotting analysis were carried out to assess the levels of MATN1-AS1, RELA, ERK1/2, Bcl-2, Bax, survivin, and MMP-9 in GBM cells. Biological functions of MATN1-AS1 in GBM tumors were measured both in vivo and in vitro. The mechanism of RELA regulation by MATN1-AS1 was detected using RNA pull-down, RNA-binding protein immunoprecipitation, chromatin immunoprecipitation, and the dual luciferase reporter gene assay. MATN1-AS1 was the most downregulated lncRNA in GBM and was correlated with a shorter survival time and poorer prognosis of GBM patients. Conversely, RELA was increased in GBM tumor tissues and negatively correlated with MATN1-AS1 expression. MATN1-AS1 over-expression or siRNA-RELA knockdown resulted in downregulation of mRNA and protein levels of RELA, ERK1/2, Bcl-2, survivin, and MMP-9; reduced cell proliferation and invasion; increased Bax mRNA and protein levels; and enhanced cellular apoptosis. MATN1-AS1 bound to E2F6, which negatively targeted RELA. Furthermore, MATN1-AS1 over-expression in GBM cells resulted in significant inhibition of tumor growth in vivo. Upregulation of the lncRNA MATN1-AS1 inhibited GBM cell proliferation and invasion through inhibition of RELA via E2F6 and suppression of the MAPK signaling pathway. MATN1-AS1 might be an underlying therapeutic target for GBM.