Wnt/β-catenin pathway transactivates microRNA-150 that promotes EMT of colorectal cancer cells by suppressing CREB signaling
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Yan-Hua Guo1,3,*, Lu-Qin Wang1,*, Bin Li1,*, Hui Xu1, Jian-Hua Yang1, Li-Si Zheng1, Peng Yu1, Ai-Dong Zhou2, Yin Zhang1, Shu-Juan Xie1, Zi-Rui Liang1, Chen-Min Zhang1, Hui Zhou1, Liang-Hu Qu1
1Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, P. R. China
2Present address: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
3Present address: Guangzhou Quality Supervision and Testing Institute, Guangzhou, China
*These authors have contributed equally to this work
Liang-Hu Qu, email: email@example.com
Keywords: Wnt/β-catenin, miR-150, CREB, EMT, colorectal cancer
Received: December 16, 2015 Accepted: May 09, 2016 Published: June 7, 2016
A hallmark of aberrant activation of the Wnt/β-catenin signaling pathway has been observed in most colorectal cancers (CRC), but little is known about the role of non-coding RNAs regulated by this pathway. Here, we found that miR-150 was the most significantly upregulated microRNA responsive to elevated of Wnt/β-catenin signaling activity in both HCT116 and HEK293T cells. Mechanistically, the β-catenin/LEF1 complex binds to the conserved TCF/LEF1-binding element in the miR-150 promoter and thereby transactivates its expression. Enforced expression of miR-150 in HCT116 cell line transformed cells into a spindle shape with higher migration and invasion activity. miR-150 markedly suppressed the CREB signaling pathway by targeting its core transcription factors CREB1 and EP300. Knockdown of CREB1 or EP300 and knockout of CREB1 by CRISPR/Cas9 phenocopied the epithelial-mesenchymal transition (EMT) observed in HCT116 cells in response to miR-150 overexpression. In summary, our data indicate that miR-150 is a novel Wnt effector that may significantly enhance EMT of CRC cells by targeting the CREB signaling pathway.
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