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

doi:10.1186/s13046-021-02129-9

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	Super-enhancer-associated TMEM44-AS1 aggravated glioma progression by forming a positive feedback loop with Myc
	Bian,Erbao 1,2; Chen,Xueran 3,4; Cheng,Li 5; Cheng,Meng 1,2; Chen,Zhigang 1,2; Yue,Xiaoyu 1,2; Zhang,Zhengwei 1,2; Chen,Jie 1,2; Sun,Libo 1,2; Huang,Kebing 1,2; Huang,Cheng 5; Fang,Zhiyou 3,4; Zhao,Bing 1,2; Li,Jun 5
	2021-10-25
发表期刊	Journal of Experimental & Clinical Cancer Research
通讯作者	Bian,Erbao(bianerbao@ahmu.edu.cn) ; Fang,Zhiyou(z.fang@cmpt.ac.cn) ; Zhao,Bing(aydzhb@126.com) ; Li,Jun(lj@ahmu.edu.cn)
摘要	AbstractBackgroundLong 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.MethodsRNA 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.ResultsWe 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.ConclusionsOur study implicates a crucial role of the TMEM44-AS1-Myc axis in glioma progression and provides a possible anti-glioma therapeutic agent.
关键词	Glioma lncRNA TMEM44-AS1 Super-enhancer Myc
DOI	10.1186/s13046-021-02129-9
语种	英语
WOS记录号	BMC:10.1186/s13046-021-02129-9
出版者	BioMed Central
引用统计
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/125662
专题	中国科学院合肥物质科学研究院
通讯作者	Bian,Erbao; Fang,Zhiyou; Zhao,Bing; Li,Jun
作者单位	1.The Second Affiliated Hospital of Anhui Medical University; Department of Neurosurgery 2.Anhui Medical University; Cerebral Vascular Disease Research Center 3.Chinese Academy of Sciences; Department of Laboratory Medicine, Hefei Cancer Hospital 4.Hefei Institutes of Physical Science, Chinese Academy of Sciences; Anhui Province Key Laboratory of Medical Physics and Technology; Institute of Health and Medical Technology 5.Anhui Medical University; School of pharmacy
推荐引用方式 GB/T 7714	Bian,Erbao,Chen,Xueran,Cheng,Li,et al. Super-enhancer-associated TMEM44-AS1 aggravated glioma progression by forming a positive feedback loop with Myc[J]. Journal of Experimental & Clinical Cancer Research,2021,40.
APA	Bian,Erbao.,Chen,Xueran.,Cheng,Li.,Cheng,Meng.,Chen,Zhigang.,...&Li,Jun.(2021).Super-enhancer-associated TMEM44-AS1 aggravated glioma progression by forming a positive feedback loop with Myc.Journal of Experimental & Clinical Cancer Research,40.
MLA	Bian,Erbao,et al."Super-enhancer-associated TMEM44-AS1 aggravated glioma progression by forming a positive feedback loop with Myc".Journal of Experimental & Clinical Cancer Research 40(2021).