Oncotarget

Research Papers:

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

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

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Oncotarget. 2017; 8:11356-11371. https://doi.org/10.18632/oncotarget.14529

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Abstract

Xixian Ke1, Yue Yuan1, Chenglin Guo2, Yan Yang1, Qiang Pu2, Xueting Hu1, Kui Tang1, Xinmei Luo1, Qianqian Jiang1, Xiaolan Su1, Lunxu Liu2, Wen Zhu1, Yuquan Wei1

1State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

2Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

Correspondence to:

Wen Zhu, email: [email protected]

Lunxu Liu, email: [email protected]

Keywords: miR-410, stemness, Wnt/β-catenin, non-small cells lung cancer

Received: June 06, 2016     Accepted: December 27, 2016     Published: January 05, 2017

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.


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