FUS/circ_002136/miR-138-5p/SOX13 feedback loop regulates angiogenesis in Glioma

血管生成 胶质瘤 染色质免疫沉淀 RNA结合蛋白 癌症研究 核糖核酸 基因沉默 化学 生物 分子生物学 细胞生物学 小RNA 基因表达 基因 发起人 生物化学
作者
Zhenwei He,Xuelei Ruan,Xiaobai Liu,Jian Zheng,Yunhui Liu,Libo Liu,Jun Ma,Lianqi Shao,Di Wang,Shuyuan Shen,Chunqing Yang,Yixue Xue
出处
期刊:Journal of Experimental & Clinical Cancer Research [Springer Nature]
卷期号:38 (1) 被引量:126
标识
DOI:10.1186/s13046-019-1065-7
摘要

Angiogenesis plays a critical role in the progression of glioma. Previous studies have indicated that RNA-binding proteins (RBPs) interact with RNAs and participate in the regulation of the malignant behaviors of tumors. As a type of endogenous non-coding RNAs, circular RNAs (circRNAs) are abnormally expressed in various cancers and are involved in diverse tumorigeneses including angiogenesis. The expression levels of FUS, circ_002136, miR-138-5p, SOX13, and SPON2 were determined using quantitative real-time PCR (qRT-PCR) and western blot. Transient cell transfection was performed using the Lipofectamine 3000 reagent. The RNA-binding protein immunoprecipitation (RNA-IP) and the RNA pull-down assays were used to detect the interaction between FUS and circ_002136. The dual-luciferase reporter assay system was performed to detect the binding sites of circ_002136 and miR-138-5p, miR-138-5p and SOX13. The chromatin immunoprecipitation (ChIP) assays were used to examine the interactions between transcription factor SOX13 and its target proteins . We demonstrated that down-regulation of FUS or circ_002136 dramatically inhibited the viability, migration and tube formation of U87 glioma-exposed endothelial cells (GECs). MiR-138-5p was down-regulated in GECs and circ_002136 functionally targeted miR-138-5p in an RNA-induced silencing complex (RISC). Inhibition of circ_002136, combined with the restoration of miR-138-5p, robustly reduced the angiogenesis of GECs. As a target gene of miR-138-5p, SOX13 was overexpressed in GECs and was proved to be involved in circ_002136 and miR-138-5p-mediated angiogenesis in gliomas. In addition, we found that SOX13 was directly associated with and activated the SPON2 promoter, thereby up-regulating the expression of SPON2 at the transcriptional level. Knockdown of SPON2 suppressed the angiogenesis in GECs. More important, SOX13 activated the FUS promoter and increased its expression, forming a feedback loop. Our data suggests that the feedback loop of FUS/circ_002136/miR-138-5p/SOX13 played a crucial role in the regulation of angiogenesis in glioma. This also provides a potential target and an alternative strategy for combined glioma therapy.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
繁荣的柏柳完成签到,获得积分10
3秒前
Tingshan完成签到,获得积分10
5秒前
清秀迎松完成签到,获得积分10
10秒前
绿色植物完成签到,获得积分10
10秒前
19秒前
庄怀逸完成签到 ,获得积分10
19秒前
芝芝莓莓完成签到,获得积分10
20秒前
清爽的凤完成签到,获得积分10
24秒前
李东东完成签到 ,获得积分10
24秒前
CHEM_XIE完成签到,获得积分10
25秒前
roking完成签到,获得积分10
25秒前
28秒前
科研通AI2S应助清爽的凤采纳,获得10
30秒前
自觉的傥完成签到,获得积分10
30秒前
东东呀完成签到,获得积分10
30秒前
不要再忘登陆密码了完成签到,获得积分10
31秒前
狂野乌冬面完成签到 ,获得积分10
31秒前
复杂觅海完成签到 ,获得积分10
33秒前
雨晴完成签到,获得积分10
34秒前
燕子完成签到,获得积分10
35秒前
上善若水呦完成签到 ,获得积分10
36秒前
枫林摇曳完成签到 ,获得积分10
36秒前
清爽的诗云完成签到 ,获得积分10
39秒前
危机的泥猴桃完成签到 ,获得积分10
40秒前
mp5完成签到,获得积分10
41秒前
Tangyartie完成签到 ,获得积分10
41秒前
42秒前
ambrose37完成签到 ,获得积分10
43秒前
悄悄是心上的肖肖完成签到 ,获得积分10
44秒前
天天快乐应助科研通管家采纳,获得10
52秒前
酷波er应助科研通管家采纳,获得10
52秒前
思源应助科研通管家采纳,获得10
52秒前
海阔天空完成签到 ,获得积分10
52秒前
冷傲的慕凝完成签到 ,获得积分10
54秒前
小九的呀完成签到 ,获得积分10
57秒前
无言完成签到 ,获得积分10
57秒前
整齐泥猴桃完成签到 ,获得积分10
58秒前
59秒前
机灵安白完成签到 ,获得积分10
59秒前
高分求助中
Rock-Forming Minerals, Volume 3C, Sheet Silicates: Clay Minerals 2000
The late Devonian Standard Conodont Zonation 2000
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 2000
The Lali Section: An Excellent Reference Section for Upper - Devonian in South China 1500
Very-high-order BVD Schemes Using β-variable THINC Method 930
The Healthy Socialist Life in Maoist China 600
The Vladimirov Diaries [by Peter Vladimirov] 600
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3265693
求助须知:如何正确求助?哪些是违规求助? 2905635
关于积分的说明 8334284
捐赠科研通 2575918
什么是DOI,文献DOI怎么找? 1400253
科研通“疑难数据库(出版商)”最低求助积分说明 654712
邀请新用户注册赠送积分活动 633554