Han Na, Yang Li, Zhang Xiaoxi, Zhou Yangmei, Chen Rui, Yu Yang, Dong Zhen, Zhang Mengxian
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Ann Transl Med. 2019 Dec;7(23):784. doi: 10.21037/atm.2019.11.36.
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 and . 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 .
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.
胶质母细胞瘤（GBM）是最具侵袭性和恶性的肿瘤类型之一。尽管治疗取得了进展，但GBM的发病机制仍 largely未知。MATN1-AS1是一种内含子保留的长链非编码RNA（lncRNA），与GBM的发展有关。然而，其潜在机制尚未确定。本研究旨在检测MATN1-AS1的表达，并揭示其在GBM中的作用。
通过分析脑胶质瘤相关基因筛选出低表达的lncRNAs。使用RT-qPCR对75例GBM肿瘤和10例正常脑组织中MATN1-AS1的相对mRNA水平进行定量。采用Kaplan-Meier法评估总生存期。进行RT-qPCR和免疫印迹分析，以评估GBM细胞中MATN1-AS1、RELA、ERK1/2、Bcl-2、Bax、survivin和MMP-9的水平。检测MATN1-AS1在GBM肿瘤中的生物学功能。使用RNA下拉、RNA结合蛋白免疫沉淀、染色质免疫沉淀和双荧光素酶报告基因检测法检测MATN1-AS1对RELA的调控机制。
MATN1-AS1是GBM中表达下调最明显的lncRNA，与GBM患者较短的生存时间和较差的预后相关。相反，RELA在GBM肿瘤组织中升高，与MATN1-AS1表达呈负相关。MATN1-AS1过表达或siRNA-RELA敲低导致RELA、ERK1/2、Bcl-2、survivin和MMP-9的mRNA和蛋白水平下调；细胞增殖和侵袭减少；Bax mRNA和蛋白水平增加；细胞凋亡增强。MATN1-AS1与E2F6结合，E2F6对RELA具有负向靶向作用。此外，GBM细胞中MATN1-AS1过表达导致肿瘤生长受到显著抑制。
lncRNA MATN1-AS1的上调通过E2F6抑制RELA并抑制MAPK信号通路，从而抑制GBM细胞的增殖和侵袭。MATN1-AS1可能是GBM的潜在治疗靶点。
