期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 128, 期 4, 页码 1267-1282出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI97225
关键词
-
资金
- NIH [R01 CA181184, P30 CA125123]
- NIH Lung Cancer SPORE [P50 CA70907, K08 CA151661]
- Department of Defense PROSPECT [W81XWH-07-1-0306]
- Cancer Prevention Research Institute of Texas Multi-investigator Research Award [RP120713]
- Jeanne F. Shelby Scholarship Fund
Epithelial tumor cells undergo epithelial-to-mesenchymal transition (EMT) to gain metastatic activity. Competing endogenous RNAs (ceRNAs) have binding sites for a common set of microRNAs (miRs) and regulate each other's expression by sponging miRs. Here, we address whether ceRNAs govern metastasis driven by the EMT-activating transcription factor ZEB1. High miR-181b levels were correlated with an improved prognosis in human lung adenocarcinomas, and metastatic tumor cell lines derived from a murine lung adenocarcinoma model in which metastasis is ZEB1-driven were enriched in miR-181b targets. ZEB1 relieved a strong basal repression of a 1 integrin (ITGA1) mRNA, which in turn upregulated adenylyl cyclase 9 mRNA (ADCY9) by sponging miR181b. Ectopic expression of the ITGA1 3'-untranslated region reversed miR-181b-mediated metastasis suppression and increased the levels of adenylyl cyclase 9 protein (AC9), which promoted tumor cell migration and metastasis. In human lung adenocarcinomas, ITGA1 and ADCY9 levels were positively correlated, and an AC9-activated transcriptomic signature had poor-prognostic value. Thus, ZEB1 initiates a miR-181b-regulated ceRNA network to drive metastasis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据