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缺氧诱导的 USP22-BMI1 轴通过调节 HIF-1α 促进胶质瘤干细胞的干性和恶性。

Hypoxia-induced USP22-BMI1 axis promotes the stemness and malignancy of glioma stem cells via regulation of HIF-1α.

机构信息

The Neurosurgery Department of the Shanghai General Hospital, Shanghai Jiaotong University, No. 85 Wujin Road, Hongkou District, Shanghai, PR China; The Neurosurgery Department of the 960th Hospital of Joint Logistics Support Force, The Chinese People's Liberation Army, No. 25 Shifan Road, Beicun Street, Worker's New Village, Tianqiao District, Jinan, Shandong Province, PR China.

The Neurosurgery Department of the 960th Hospital of Joint Logistics Support Force, The Chinese People's Liberation Army, No. 25 Shifan Road, Beicun Street, Worker's New Village, Tianqiao District, Jinan, Shandong Province, PR China.

出版信息

Life Sci. 2020 Apr 15;247:117438. doi: 10.1016/j.lfs.2020.117438. Epub 2020 Feb 15.

DOI:10.1016/j.lfs.2020.117438
PMID:32070708
Abstract

AIMS

This study intends to investigate the mechanisms of ubiqutin-specific protease 22 (USP22)/B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) on the biological phenotypes of glioma stem cells (GSCs) under hypoxia.

MAIN METHODS

Western blot, Cell Counting Kit-8, colony formation and flow cytometry assays were preformed to evaluate cells biological behaviors. Luciferase assay was utilized to identify the associations among USP22, HIF-1α and BMI1.

KEY FINDINGS

Silencing USP22 reduced the stemness and proliferation of GSCs, and increased its apoptosis in response to hypoxia. Whilst, overexpression of BMI1 reversed these phenomena. Whilst, a significant decrease in proliferation and stemness of GSCs caused by HIF-1α exhaustion were inversed by overexpression of USP22 or BMI1.

SIGNIFICANCE

Function of USP22-BMI1 on biological behaviors of GSCs was regulated by HIF-1α in response to hypoxia.

摘要

目的

本研究旨在探讨泛素特异性蛋白酶 22(USP22)/B 细胞特异性莫洛尼鼠白血病病毒整合位点 1(BMI1)在缺氧条件下对神经胶质瘤干细胞(GSCs)生物学表型的作用机制。

主要方法

采用 Western blot、细胞计数试剂盒-8、集落形成和流式细胞术检测细胞的生物学行为。利用荧光素酶报告基因检测实验鉴定 USP22、HIF-1α 和 BMI1 之间的关联。

主要发现

沉默 USP22 可降低 GSCs 的干性和增殖能力,并增加其在缺氧条件下的凋亡。而过表达 BMI1 则逆转了这些现象。而 HIF-1α 耗竭导致 GSCs 的增殖和干性显著降低,过表达 USP22 或 BMI1 则可逆转这一现象。

意义

USP22-BMI1 在缺氧条件下对 GSCs 生物学行为的作用是由 HIF-1α 调节的。

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