title: Aberrantly expressed miR-582-3p maintains lung cancer stem cell-like traits by activating Wnt/β-catenin signalling.
abstract: Cancer stem cells (CSCs) are involved in tumorigenesis, tumour recurrence and therapy resistance and Wnt signalling is essential for the development of the biological traits of CSCs. In non-small cell lung carcinoma (NSCLC), unlike in colon cancer, mutations in β-catenin and APC genes are uncommon; thus, the mechanism underlying the constitutive activation of Wnt signalling in NSCLC remains unclear. Here we report that miR-582-3p expression correlates with the overall- and recurrence-free-survival of NSCLC patients, and miR-582-3p has an activating effect on Wnt/β-catenin signalling. miR-582-3p overexpression simultaneously targets multiple negative regulators of the Wnt/β-catenin pathway, namely, AXIN2, DKK3 and SFRP1. Consequently, miR-582-3p promotes CSC traits of NSCLC cells in vitro and tumorigenesis and tumour recurrence in vivo. Antagonizing miR-582-3p potently inhibits tumour initiation and progression in xenografted animal models. These findings suggest that miR-582-3p mediates the constitutive activation of Wnt/β-catenin signalling, likely serving as a potential therapeutic target for NSCLC.
authors.affiliation: Department of Microbiology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong 510080, China.
authors.forename: Lishan
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Microbiology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong 510080, China.
authors.forename: Junchao
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Microbiology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong 510080, China.
authors.forename: Baixue
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong 510080, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Microbiology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong 510080, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Microbiology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong 510080, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong 510080, China.|Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Microbiology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong 510080, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Microbiology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong 510080, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong 510080, China.|Key Laboratory of Functional Molecules from Oceanic Microorganisms, Sun Yat-sen University, Department of Education of Guangdong Province, Guangzhou, Guangdong 510080, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Microbiology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong 510080, China.
authors.forename: Jueheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Microbiology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong 510080, China.
authors.forename: Mengfeng
authors.initials: M
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D060466:Axin Protein / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D018925:Chemokines; D002681:China / Q000453:epidemiology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000502:physiology*; D010641:Phenotype; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; D051153:Wnt Proteins; D051176:beta Catenin; C491761:AXIN2 protein, human; C498624:DKK3 protein, human; C000593706:MIRN582 microRNA, human; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins