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miR-30过表达通过调节Jak/STAT3信号通路促进胶质瘤干细胞。

miR-30 overexpression promotes glioma stem cells by regulating Jak/STAT3 signaling pathway.

作者信息

Che Shusheng, Sun Tingting, Wang Jianpeng, Jiao Yingbin, Wang Chao, Meng Qinghai, Qi Weiguo, Yan Zhiyong

机构信息

Department of Neurosurgery, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong, 266003, China.

Intensive Care Unit, Qingdao Municipal Hospital, Qingdao, Shandong, 266011, China.

出版信息

Tumour Biol. 2015 Sep;36(9):6805-11. doi: 10.1007/s13277-015-3400-8. Epub 2015 Apr 4.

Abstract

Malignant glioma is the most common intracranial tumor with poor prognosis. It is well believed that glioma stem cells (GSCs) are responsible for the initiation and progression of glioma. Janus kinase/signal transducer and activator of transcription (Jak/STAT3) pathway plays a key role in the functions of GSCs. However, the regulatory mechanism of Jak/STAT3 pathway has not been completely elucidated. This study employed multidisciplinary approaches to investigate the upstream regulators of Jak/STAT3 signaling in GSCs. miR-30 was found to be overexpressed in the GSCs derived from U-87 MG and primary glioma cells, compared with non-stem-cell-like glioma cells and normal cells. Downregulation of miR-30 was able to suppress Jak/STAT3 pathway and reduce the tumorigenecity of GSCs. miR-30 decreased the expression of suppressor of cytokine signaling 3 (SOCS3) expression by targeting 3'UTR of its mRNA. The silencing of SOCS3 abolished the effect of miR-30 downregulation on GSCs. Collectively, there is a regulatory pathway consisting of miR-30, SOCS3, and Jak/STAT3 in GSCs, and targeting this pathway may be a promising strategy to treat glioma.

摘要

恶性胶质瘤是最常见的颅内肿瘤,预后较差。人们普遍认为,胶质瘤干细胞(GSCs)是胶质瘤发生和进展的原因。Janus激酶/信号转导和转录激活因子(Jak/STAT3)通路在GSCs的功能中起关键作用。然而,Jak/STAT3通路的调控机制尚未完全阐明。本研究采用多学科方法研究GSCs中Jak/STAT3信号的上游调节因子。与非干细胞样胶质瘤细胞和正常细胞相比,发现miR-30在源自U-87 MG和原发性胶质瘤细胞的GSCs中过表达。下调miR-30能够抑制Jak/STAT3通路并降低GSCs的致瘤性。miR-30通过靶向细胞因子信号转导抑制因子3(SOCS3)mRNA的3'UTR来降低其表达。沉默SOCS3消除了miR-30下调对GSCs的影响。总的来说,GSCs中存在由miR-30、SOCS3和Jak/STAT3组成的调控通路,靶向该通路可能是治疗胶质瘤的一种有前景的策略。

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