Resistin promotes tumor metastasis by down-regulation of miR-519d through the AMPK/p38 signaling pathway in human chondrosarcoma cells
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Chun-Hao Tsai1,2,*, Hsiao-Chi Tsai3,*, Ho-Ning Huang4, Chih-Hung Hung2, Chin-Jung Hsu2,5, Yi-Chin Fong2,5, Horng-Chaung Hsu1,2, Yuan-Li Huang4 and Chih-Hsin Tang3,4,6
1 Department of Medicine and Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
2 Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
3 Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
4 Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
5 School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
6 Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
* These authors contributed equally to this work
Chih-Hsin Tang , email:
Yuan-Li Huang , email:
Keywords: Chondrosarcoma; MicroRNA; MMP; Resistin; Metastasis
Received: September 05, 2014 Accepted: November 06, 2014 Published: November 06, 2014
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.
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