Author:
Zhao Junshuang,Jiang Yang,Zhang Haiying,Zhou Jinpeng,Chen Lian,Li Hao,Xu Jinkun,Zhang Guoqing,Jing Zhitao
Abstract
Abstract
Background
Glioma is the most common and malignant tumor of central nervous system. The tumor initiation, self-renewal, and multi-lineage differentiation abilities of glioma stem cells (GSCs) are responsible for glioma proliferation and recurrence. Although circular RNAs (circRNAs) play vital roles in the progression of glioma, the detailed mechanisms remain unknown.
Methods
qRT-PCR, western blotting, immunohistochemistry, and bioinformatic analysis were performed to detect the expression of circATP5B, miR-185-5p, HOXB5, and SRSF1. Patient-derived GSCs were established, and MTS, EDU, neurosphere formation, and limiting dilution assays were used to detect the proliferation of GSCs. RNA-binding protein immunoprecipitation, RNA pull-down, luciferase reporter assays, and chromatin immunoprecipitation assays were used to detect these molecules’ regulation mechanisms.
Results
We found circATP5B expression was significantly upregulated in GSCs and promoted the proliferation of GSCs. Mechanistically, circATP5B acted as miR-185-5p sponge to upregulate HOXB5 expression. HOXB5 was overexpressed in glioma and transcriptionally regulated IL6 expression and promoted the proliferation of GSCs via JAK2/STAT3 signaling. Moreover, RNA binding protein SRSF1 could bind to and promote circATP5B expression and regulate the proliferation of GSCs, while HOXB5 also transcriptionally regulated SRSF1 expression.
Conclusions
Our study identified the SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop in GSCs. This provides an effective biomarker for glioma diagnosis and prognostic evaluation.
Funder
National Natural Science Foundation of China
the Major Disease Prevention and Control Technology Action Plan of China
the Liaoning BaiQianWan Talents Program
the Social Development Program from Shenyang Science and Technology Bureau, China
the Project of JiangSu XianSheng Pharmaceutical Co.
Publisher
Springer Science and Business Media LLC
Cited by
28 articles.
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