Unknown

Dataset Information

0

The epithelial-to-mesenchymal transition activator ZEB1 initiates a prometastatic competing endogenous RNA network.


ABSTRACT: 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 ?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.

SUBMITTER: Tan X 

PROVIDER: S-EPMC5873879 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC3614934 | biostudies-literature
| S-EPMC5135094 | biostudies-literature
| S-EPMC2507753 | biostudies-literature
| S-EPMC3228467 | biostudies-other
| S-EPMC5004933 | biostudies-literature
| S-EPMC6804631 | biostudies-literature
| S-EPMC7598708 | biostudies-literature
| S-EPMC6413055 | biostudies-literature
| S-EPMC6393568 | biostudies-literature
| S-EPMC3092351 | biostudies-literature