https://scholars.lib.ntu.edu.tw/handle/123456789/632107
標題: | ADAM9 enhances CDCP1 by inhibiting miR-1 through EGFR signaling activation in lung cancer metastasis | 作者: | Chiu K.-L Lin Y.-S Kuo T.-T Lo C.-C Huang Y.-K Chang H.-F ERIC YAO-YU CHUANG Lin C.-C Cheng W.-C Liu Y.-N LIANG-CHUAN LAI Sher Y.-P. |
關鍵字: | ADAM9; CDCP1; EGFR; Lung cancer; MiR-1 | 公開日期: | 2017 | 卷: | 8 | 期: | 29 | 起(迄)頁: | 47365-47378 | 來源出版物: | Oncotarget | 摘要: | MicroRNAs (miRNAs), which are endogenous short noncoding RNAs, can regulate genes involved in important biological and pathological functions. Therefore, dysregulation of miRNAs plays a critical role in cancer progression. However, whether the aberrant expression of miRNAs is regulated by oncogenes remains unclear. We previously demonstrated that a disintegrin and metalloprotease domain 9 (ADAM9) promotes lung metastasis by enhancing the expression of a pro-migratory protein, CUB domain containing protein 1 (CDCP1). In this study, we found that this process occurred via miR-1 down-regulation. miR-1 expression was down-regulated in lung tumors, but increased in ADAM9-knockdown lung cancer cells, and was negatively correlated with CDCP1 expression as well as the migration ability of lung cancer cells. Luciferase-based reporter assays showed that miR-1 directly bound to the 3'-untranslated region of CDCP1 and inhibited its translation. Treatment with a miR-1 inhibitor restored CDCP1 protein levels and enhanced tumor cell mobility. Overexpression of miR-1 decreased tumor metastases and increased the survival rate in mice. ADAM9 knockdown reduced EGFR signaling and increased miR-1 expression. These results revealed that ADAM9 down-regulates miR-1 via activating EGFR signaling pathways, which in turn enhances CDCP1 expression to promote lung cancer progression. © Chiu et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85024387492&doi=10.18632%2foncotarget.17648&partnerID=40&md5=287e95f996ffd758c2e9b1f702c36e82 https://scholars.lib.ntu.edu.tw/handle/123456789/632107 |
ISSN: | 19492553 | DOI: | 10.18632/oncotarget.17648 | SDG/關鍵字: | ADAM9 protein; CDCP1 protein; epidermal growth factor receptor; microRNA 1; oncoprotein; unclassified drug; 3' untranslated region; animal experiment; animal model; Article; cancer survival; cell migration; cell motility; controlled study; down regulation; gene overexpression; human; human cell; luciferase assay; lung cancer cell line; lung metastasis; molecular pathology; nonhuman; protein expression; protein protein interaction; protein targeting; signal transduction; survival rate |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。