title: Resistin promotes tumor metastasis by down-regulation of miR-519d through the AMPK/p38 signaling pathway in human chondrosarcoma cells.
abstract: Resistin is a recently discovered adipocyte-secreting adipokine, which may play a critical role in modulating cancer pathogenesis. Chondrosarcoma is a highly malignant tumor known to frequently metastasize; however, the role of resistin in the metastasis of human chondrosarcoma is largely unknown. Here, we found that the expression of resistin was higher in chondrosarcoma biopsy tissues than in normal cartilage. Moreover, treatment with resistin increased matrix metalloproteinase (MMP)-2 expression and promoted cell migration in human chondrosarcoma cells. Co-transfection with microRNA (miR)-519d mimic resulted in reversed resistin-mediated cell migration and MMP-2 expression. Additionally, AMP-activated protein kinase (AMPK) and p38 inhibitors or siRNAs reduced the resistin-increased cell migration and miR-519d suppression, and inhibition of resistin expression resulted in suppression of MMP-2 expression and lung metastasis in vivo. Taken together, our results indicate that resistin promotes chondrosarcoma metastasis and MMP-2 expression through activation of the AMPK/p38 signaling pathway and down-regulation of miR-519d expression. Therefore, resistin may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis.
authors.affiliation: Department of Medicine and Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan. Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Hsiao-Chi
authors.initials: HC
authors.lastname: Tsai
authors.affiliation: Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
authors.forename: Ho-Ning
authors.initials: HN
authors.lastname: Huang
authors.affiliation: Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hung
authors.affiliation: Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan. School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chin-Jung
authors.initials: CJ
authors.lastname: Hsu
authors.affiliation: Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan. School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Fong
authors.affiliation: Department of Medicine and Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan. Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Horng-Chaung
authors.initials: HC
authors.lastname: Hsu
authors.affiliation: Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
authors.forename: Yuan-Li
authors.initials: YL
authors.lastname: Huang
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan. Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan. Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism*; D002465:Cell Movement; D002813:Chondrosarcoma / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000378:metabolism; D052243:Resistin / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C546194:MIRN519 microRNA, human; D035683:MicroRNAs; C499624:RETN protein, human; D034741:RNA, Small Interfering; D052243:Resistin; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2