title: MiR-410 induces stemness by inhibiting Gsk3β but upregulating β-catenin in non-small cells lung cancer.
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.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Xixian
authors.initials: X
authors.lastname: Ke
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Xueting
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Lunxu
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta / Q000096:biosynthesis* / Q000235:genetics; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C495270:CTNNB1 protein, human; C568527:MIRN410 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta
keywords: Wnt/β-catenin; miR-410; non-small cells lung cancer; stemness