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在非小细胞肺癌中,微小RNA-410通过抑制糖原合成酶激酶3β但上调β-连环蛋白来诱导干性。

MiR-410 induces stemness by inhibiting Gsk3β but upregulating β-catenin in non-small cells lung cancer.

作者信息

Ke Xixian, Yuan Yue, Guo Chenglin, Yang Yan, Pu Qiang, Hu Xueting, Tang Kui, Luo Xinmei, Jiang Qianqian, Su Xiaolan, Liu Lunxu, Zhu Wen, Wei Yuquan

机构信息

State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

出版信息

Oncotarget. 2017 Feb 14;8(7):11356-11371. doi: 10.18632/oncotarget.14529.

Abstract

Our previous research indicated miR-410 played a critical role in promoting the tumorigenesis and development of NSCLC (non-small cells lung cancer). MiR-410 has been recently reported to be crucial for development and differentiation of embryonic stem cells. But it remains elusive whether miR-410 stimulates the stemness of cancer until now. Herein, we identify miR-410 induces the stemness and is associated with the progression of NSCLC. We demonstrate miR-410 increases the levels of stem cells marker Sox2, Oct4, Nanog, CXCR4 as well as lung cancer stem cells surface marker CD44 and CD166. MiR-410 promotes stem cells-like properties such as proliferation, sphere formation, metastasis and chemoresistance. Moreover, Gsk3β is directly targeted and post-transcriptionally downregulated by miR-410. Also, the expression levels of miR-410 and Gsk3β may be correlated to clinicopathological differentiation in NSCLC tumor specimens. Additionally, we demonstrate miR-410 induces stemness through inhibiting Gsk3β but increasing Sox2, Oct4, Nanog and CXCR4, which binds to β-catenin signaling. In conclusion, our findings identify the miR-410/Gsk3β/β-catenin signaling axis is a novel molecular circuit in inducing stemness of NSCLC.

摘要

我们之前的研究表明,miR-410在促进非小细胞肺癌(NSCLC)的肿瘤发生和发展中起关键作用。最近有报道称,miR-410对胚胎干细胞的发育和分化至关重要。但截至目前,miR-410是否刺激癌症的干性仍不清楚。在此,我们确定miR-410诱导干性并与NSCLC的进展相关。我们证明miR-410可提高干细胞标志物Sox2、Oct4、Nanog、CXCR4以及肺癌干细胞表面标志物CD44和CD166的水平。miR-410促进干细胞样特性,如增殖、成球、转移和化疗耐药性。此外,Gsk3β是miR-410的直接靶点,并在转录后被下调。而且,miR-410和Gsk3β的表达水平可能与NSCLC肿瘤标本中的临床病理分化相关。此外,我们证明miR-410通过抑制Gsk3β但增加与β-连环蛋白信号通路结合的Sox2、Oct4、Nanog和CXCR4来诱导干性。总之,我们的研究结果确定了miR-410/Gsk3β/β-连环蛋白信号轴是诱导NSCLC干性的一种新型分子回路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85d0/5355270/c73d3e428ac9/oncotarget-08-11356-g001.jpg

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