https://scholars.lib.ntu.edu.tw/handle/123456789/563156
標題: | miR-519d promotes melanoma progression by downregulating EphA4 | 作者: | KUO-TAI HUA Hong J.-B. YI-SHUAN SHEEN Huang H.-Y. Huang Y.-L. JAU-SHIUH CHEN YI-HUA LIAO |
公開日期: | 2018 | 出版社: | American Association for Cancer Research Inc. | 卷: | 78 | 期: | 1 | 起(迄)頁: | 216-229 | 來源出版物: | Cancer Research | 摘要: | Increasing evidence suggests that there is a unique cell subpopulation in melanoma that can form nonadherent melanospheres in serum-free stem cell medium, mimicking aggressive malignancy. Using melanospheres as a model to investigate progression mechanisms, we found that miR-519d overexpression was sufficient to promote cell proliferation, migration, invasion, and adhesion in vitro and lung metastatic capability in vivo. The cell adhesion receptor EphA4 was determined to be a direct target of miR-519d. Forced expression of EphA4 reversed the effects of miR-519d overexpression, whereas silencing of EphA4 phenocopied the effect of miR-519d. Malignant progression phenotypes were also affected at the level of epithelial-to-mesenchymal transition and the ERK1/2 signaling pathway inversely affected by miR-519d or EphA4 expression. In clinical specimens of metastatic melanoma, we observed significant upregulation of miR-519d and downregulation of EphA4, in the latter case correlated inversely with overall survival. Taken together, our results suggest a significant functional role for miR-519d in determining EphA4 expression and melanoma progression. Significance: These results suggest a significant role for miR-519d in determining expression of a pivotal cell adhesion molecule that may impact risks of malignant progression in many cancers. ? 2018 American Association for Cancer Research |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85040193100&doi=10.1158%2f0008-5472.CAN-17-1933&partnerID=40&md5=2eaef38ac8988ca8e376acbc653abe0f https://scholars.lib.ntu.edu.tw/handle/123456789/563156 |
ISSN: | 0008-5472 | DOI: | 10.1158/0008-5472.CAN-17-1933 | SDG/關鍵字: | cisplatin; ephrin receptor A4; microRNA; microRNA 519d; mitogen activated protein kinase 1; mitogen activated protein kinase 3; unclassified drug; ephrin receptor A4; microRNA; MIRN519 microRNA, human; animal cell; animal experiment; animal model; animal tissue; Article; cancer growth; cancer survival; carcinogenesis; cell adhesion; chemosensitivity; concentration (parameters); controlled study; correlational study; cytotoxicity; down regulation; EphA4 gene; epithelial mesenchymal transition; gene function; gene overexpression; gene silencing; human; human cell; human tissue; in vitro study; in vivo study; lung metastasis; male; MAPK signaling; melanoma; mouse; nonhuman; overall survival; phenotype; priority journal; protein expression; tumor growth; tumor invasion; upregulation; 3' untranslated region; animal; cell motion; cell proliferation; down regulation; drug screening; gene expression regulation; genetics; lung tumor; melanoma; metabolism; pathology; SCID mouse; secondary; tumor cell line; 3' Untranslated Regions; Animals; Cell Line, Tumor; Cell Movement; Cell Proliferation; Down-Regulation; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Male; Melanoma; Mice, SCID; MicroRNAs; Receptor, EphA4; Xenograft Model Antitumor Assays |
顯示於: | 毒理學研究所 |
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