MicroRNA-138 suppresses ovarian cancer cell invasion and metastasis by targeting SOX4 and HIF-1α

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題名:	MicroRNA-138 suppresses ovarian cancer cell invasion and metastasis by targeting SOX4 and HIF-1α
作者:	王陸海;Yeh, Yu-Ming;Chuang, Chi-Mu;Chao, Kuan-Chong;Wang, Lu-Hai
貢獻者:	生醫理工學院生命科學系
關鍵詞:	Cancer;Metastasis;MicroRNAs;Ovarian cancer;Tumors
日期:	2013-08-15
上傳時間:	2026-04-23 11:13:23 (UTC+8)
出版者:	Wiley-Liss Inc.;Hoboken: Wiley Subscription Services, Inc
摘要:	摘要： Metastasis is the major factor affecting patient survival in ovarian cancer. However, its molecular mechanisms remain unclear. Our study used isogenic pairs of low- and high-invasive ovarian cancer cell lines to demonstrate the downregulation of miRNA-138 in the highly invasive cells, and its functioning as an inhibitor of cell migration and invasion. An orthotopic xenograft mouse model further demonstrated that the expression of miRNA-138 inhibited ovarian cancer metastasis to other organs. Results indicated that miR-138 directly targeted SRY-related high mobility group box 4 (SOX4) and hypoxia-inducible factor-1[alpha] (HIF-1[alpha]), and overexpression of SOX4 and HIF-1[alpha] effectively reversed the miR-138-mediated suppression of cell invasion. Epidermal growth factor receptor acted as the downstream molecule of SOX4 by way of direct transcriptional control, whereas Slug was the downstream molecule of HIF-1[alpha] by way of proteasome-mediated degradation. Analysis of human ovarian tumors further revealed downregulation of miR-138 and upregulation of SOX4 in late-stage tumors. Patients with miR-138low/SOXhigh signature are predominant in late stage and tend to have malignant phenotypes including lymph nodes metastasis, larger ascites volume and higher tumor grade. Our study demonstrates the role and clinical relevance of miR-138 in ovarian cancer cell invasion and metastasis, providing a potential therapeutic strategy for suppression of ovarian cancer metastasis by targeting SOX4 and HIF-1[alpha] pathways. What's new? A microRNA (miRNA) called miR-138 is known to be down-regulated in several types of cancer. In this study, the authors found that miR-138 suppresses ovarian cancer (OvCa) metastasis in mice, by targeting two transcriptional factors, SOX4 and HIF-1[alpha]. They also found that OvCa cells with low levels of miR-138 and high SOX4 levels were associated with a highly malignant phenotype. These results identify novel signaling pathways and potential biomarkers in OvCa that may provide new therapeutic targets, as well as useful prognostic information. [PUBLICATION ABSTRACT] 出版者： Hoboken: Wiley Subscription Services, Inc 出版日期： 2013-08-15 出處： International journal of cancer, 2013-08, Vol.133 (4), p.867 資源來源： Wiley Online Library - AutoHoldings Journals 版權： Copyright © 2013 UICC 識別號： ISSN: 0020-7136 識別號： EISSN: 1097-0215 識別號： DOI: 10.1002/ijc.28086
顯示於類別:	[生命科學系] 期刊論文

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