泛素连接酶
细胞生物学
基因敲除
细胞生长
细胞周期
调节器
小RNA
抑癌基因
泛素
作者
Yang Jiang,Zhenlin Wang,Chenting Ying,Jiangfeng Hu,Tao Zeng,Liang Gao
出处
期刊:Oncogene
[Springer Nature]
日期:2021-05-20
卷期号:40 (24): 4094-4110
被引量:2
标识
DOI:10.1038/s41388-021-01833-2
摘要
Glioma is the most common and fatal primary malignant brain tumor. Glioma stem cells (GSCs) may be an important factor in glioma cell proliferation, invasion, chemoradiotherapy tolerance, and recurrence. Therefore, discovering novel GSCs related circular RNAs (circRNAs) may finds out a prospective target for the treatment of glioma. A novel circRNA-CHAF1A (circCHAF1A) was first found in our study. CircCHAF1A was overexpressed in glioma and related to the low survival rate. Functionally, it was found that no matter in vitro or in vivo, circCHAF1A can facilitate the proliferation and tumorigenesis of TP53wt GSCs. Mechanistically, circCHAF1A upregulated transcription factor HOXC8 expression in GSCs through miR-211-5p sponging. Then, HOXC8 can transcriptionally upregulate MDM2 expression and inhibited the antitumor effect of p53. Furtherly, the RNA binding protein FMR1 can bind to and promoted the expression of circCHAF1A via maintaining its stability, while HOXC8 also transcribed the FMR1 expression to form a feedback loop, which may be involved in the malignant transformation of glioma. The novel feedback loop among FMR1, circCHAF1A, miR-211-5p, and HOXC8 in GSCs can facilitate the proliferation and tumorigenesis of glioma and GSCs. It also provided a helpful biomarker for diagnosis and prognostic evaluation of glioma and may be applied to molecular targeted therapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI