中山醫學大學機構典藏 CSMUIR:Item 310902500/24708
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    题名: Melatonin-triggered post-transcriptional and post-translational modifications of ADAMTS1 coordinately retard tumorigenesis and metastasis of renal cell carcinoma
    作者: Wen, YC;Lin, YW;Chu, CY;Yang, YC;Yang, SF;Liu, YF;Hsiao, M;Lee, WJ;Chien, MH
    关键词: ADAMTS1;melatonin;microRNA;progression;renal cell carcinoma;tissue remodeling
    日期: 2020
    上传时间: 2022-08-09T08:06:44Z (UTC)
    出版者: WILEY
    ISSN: 0742-3098
    摘要: A disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family are widely implicated in tissue remodeling events manifested in cancer development. ADAMTS1, the most fully characterized ADAMTS, plays conflicting roles in different cancer types; however, the role of ADAMTS1 in renal cell carcinoma (RCC) remains unclear. Herein, we found that ADAMTS1 is highly expressed in RCC tissues compared to normal renal tissues, and its expression was correlated with an advanced stage and a poor prognosis of RCC patients. In vitro, we observed higher expression of ADAMTS1 in metastatic (m)RCC cells compared to primary cells, and manipulation of ADAMTS1 expression affected cell invasion and clonogenicity. Results from protease array showed that ADAMTS1 is modulated by melatonin through mechanisms independent of the MT1 receptor in mRCC cells, and overexpression of ADAMTS1 relieved the invasion/clonogenicity and growth/metastasis inhibition imposed by melatonin treatment in vitro and in an orthotopic xenograft model. The human microRNA (miR) OneArray showed that miR-181d and miR-let-7f were induced by melatonin and, respectively, targeted the 3'-UTR and non-3'-UTR of ADAMTS1 to suppress its expression and mRCC invasive ability. Clinically, RCC patients with high levels of miR-181d or miR-let-7f and a low level of ADAMTS1 had the most favorable prognoses. In addition, ubiquitin/proteasome-mediated degradation of ADAMTS1 can also be triggered by melatonin. Together, our study indicates that ADAMTS1 may be a useful biomarker for predicting RCC progression. The novel convergence between melatonin and ADAMTS1 post-transcriptional and post-translational regulation provides new insights into the role of melatonin-induced molecular regulation in suppressing RCC progression.
    URI: http://dx.doi.org/10.1111/jpi.12668
    https://www.webofscience.com/wos/woscc/full-record/WOS:000537921400001
    https://ir.csmu.edu.tw:8080/handle/310902500/24708
    關聯: JOURNAL OF PINEAL RESEARCH ,2020 ,v69 ,issue 2
    显示于类别:[中山醫學大學研究成果] 期刊論文

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