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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2021 | Glioma | Research

Super-enhancer-associated TMEM44-AS1 aggravated glioma progression by forming a positive feedback loop with Myc

Authors: Erbao Bian, Xueran Chen, Li Cheng, Meng Cheng, Zhigang Chen, Xiaoyu Yue, Zhengwei Zhang, Jie Chen, Libo Sun, Kebing Huang, Cheng Huang, Zhiyou Fang, Bing Zhao, Jun Li

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

Background

Long non-coding RNAs (lncRNAs) have been considered as one type of gene expression regulator for cancer development, but it is not clear how these are regulated. This study aimed to identify a specific lncRNA that promotes glioma progression.

Methods

RNA sequencing (RNA-seq) and quantitative real-time PCR were performed to screen differentially expressed genes. CCK-8, transwell migration, invasion assays, and a mouse xenograft model were performed to determine the functions of TMEM44-AS1. Co-IP, ChIP, Dual-luciferase reporter assays, RNA pulldown, and RNA immunoprecipitation assays were performed to study the molecular mechanism of TMEM44-AS1 and the downstream target.

Results

We identified a novel lncRNA TMEM44-AS1, which was aberrantly expressed in glioma tissues, and that increased TMEM44-AS1 expression was correlated with malignant progression and poor survival for patients with glioma. Expression of TMEM44-AS1 increased the proliferation, colony formation, migration, and invasion of glioma cells. Knockdown of TMEM44-AS1 in glioma cells reduced cell proliferation, colony formation, migration and invasion, and tumor growth in a nude mouse xenograft model. Mechanistically, TMEM44-AS1 is directly bound to the SerpinB3, and sequentially activated Myc and EGR1/IL-6 signaling; Myc transcriptionally induced TMEM44-AS1 and directly bound to the promoter and super-enhancer of TMEM44-AS1, thus forming a positive feedback loop with TMEM44-AS. Further studies demonstrated that Myc interacts with MED1 regulates the super-enhancer of TMEM44-AS1. More importantly, a novel small-molecule Myc inhibitor, Myci975, alleviated TMEM44-AS1-promoted the growth of glioma cells.

Conclusions

Our study implicates a crucial role of the TMEM44-AS1-Myc axis in glioma progression and provides a possible anti-glioma therapeutic agent.

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Title: Super-enhancer-associated TMEM44-AS1 aggravated glioma progression by forming a positive feedback loop with Myc
Authors: Erbao Bian
Xueran Chen
Li Cheng
Meng Cheng
Zhigang Chen
Xiaoyu Yue
Zhengwei Zhang
Jie Chen
Libo Sun
Kebing Huang
Cheng Huang
Zhiyou Fang
Bing Zhao
Jun Li
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Glioma
Glioma
Glioma
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-02129-9

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Abstract

Background

Methods

Results

Conclusions

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