Sphingosine-1-phosphate suppresses chondrosarcoma metastasis by upregulation of tissue inhibitor of metalloproteinase 3 through suppressing miR-101 expression

ASIA unversity > 醫學暨健康學院 > 生物科技學系 > 期刊論文 > Item 310904400/108158

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题名:	Sphingosine-1-phosphate suppresses chondrosarcoma metastasis by upregulation of tissue inhibitor of metalloproteinase 3 through suppressing miR-101 expression
作者:	蔡俊灝;Chun-Hao Tsai;Dong-Ying Ya;Dong-Ying Yang;Chih-Yang Li;Chih-Yang Lin;Tsung-Ming C;Tsung-Ming Chen;湯智昕;Chih-Hsin Tang;黃元勵;HUANG, YUAN-LI
贡献者:	生物科技學系
日期:	2017-10
上传时间:	2017-10-30 02:42:07 (UTC+0)
摘要:	Chondrosarcoma is the second most common primary malignancy form of bone cancer, exhibiting resistance to chemotherapy and radiation therapy as well as developing high metastasis ability in late‐stage tumors. Thus, understanding the metastatic processes of chondrosarcoma is considered a strategy for the treatment of this disease. Sphingosine 1‐phosphate (S1P), a bioactive sphingolipid, is produced intracellularly by sphingosine kinase (SphK) and is regarded as a second signaling molecule that regulates inflammation, proliferation, angiogenesis, and metastasis. However, the effect of S1P on chondrosarcoma remains uncertain. As demonstrated by the transwell, immunoblotting, and real‐time PCR analyses, we found that S1P inhibited cell migration and MMP‐2 expression through the upregulation of the tissue inhibitor of metalloproteinase‐3 (TIMP‐3) expression in human chondrosarcoma cells. Additionally, we also showed that microRNA (miRNA)‐101, which targets the 3′ untranslated region (3′UTR) of TIMP‐3, decreased significantly following S1P treatment. After transfection with miR‐101 mimics, the S1P‐regulated cell migration and TIMP‐3 expression were both reversed. Furthermore, we also showed that the S1P‐inhibited cell migration is mediated through the c‐Src/MEK/ERK signaling axis. Meanwhile, the in vivo study indicated that overexpression of SphK1 decreases chondrosarcoma metastasis to the lungs. Our results illustrate the clinical significance between SphK1, TIMP‐3, and miR‐101 in human chondrosarcoma patients. Taken together, our results suggest that S1P and miR‐101 may prove to be potential therapeutic targets for future chondrosarcoma treatment. Keywords: chondrosarcoma, metastasis, microRNA, sphingosine‐1‐phosphate, tissue inhibitor of metalloproteinase
關聯:	Molecular Oncology
显示于类别:	[生物科技學系] 期刊論文

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