Oncotarget

Research Papers:

Wnt/β-catenin pathway transactivates microRNA-150 that promotes EMT of colorectal cancer cells by suppressing CREB signaling

Yan-Hua Guo, Lu-Qin Wang, Bin Li, Hui Xu, Jian-Hua Yang, Li-Si Zheng, Peng Yu, Ai-Dong Zhou, Yin Zhang, Shu-Juan Xie, Zi-Rui Liang, Chen-Min Zhang, Hui Zhou and Liang-Hu Qu _

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Oncotarget. 2016; 7:42513-42526. https://doi.org/10.18632/oncotarget.9893

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Abstract

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

Correspondence to:

Liang-Hu Qu, email: lssqlh@mail.sysu.edu.cn

Keywords: Wnt/β-catenin, miR-150, CREB, EMT, colorectal cancer

Received: December 16, 2015     Accepted: May 09, 2016     Published: June 7, 2016

ABSTRACT

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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