Epigenetic silencing of miR-490-3p promotes development of an aggressive colorectal cancer phenotype through activation of the Wnt/β-catenin signaling pathway
Authors: Chunhui Cui
Yuhao Luo
Fujun Shi
Qiang Li
Liang Zhao
Kehong Zheng
Wei Zheng
Xinying Zhou
Hui Wang
Zonghai Huang
Jinlong Yu
Fei Chen
Feifei Zhang
Dachuan Zhao
Zetao Shen
Zhiqun Lin
Ziyun Shao
Mingyi Li
Zhaowei Zou
Journal: Cancer Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: Colorectal cancer (CRC); Epithelial–mesenchymal transition (EMT); Frequently rearranged in advanced T-cell lymphomas protein (FRAT1); Wnt signaling pathway; miR-490-3p.
Affiliations: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China., Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China., Department of Medical Oncology, Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou, China., Radiotherapy Department, Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou, China., Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China., Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Electronic address: ., Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. Electronic address: .

Abstract:  The Wnt/β-catenin pathway is known to contribute to colorectal cancer (CRC) progression, although little is known about the contribution of β-catenin on this process. We investigated the role of miR-490-3p, which was recently reported to suppress tumorigenesis through its effect on Wnt/β-catenin signaling. We found that hypermethylation of the miR-490-3p promoter down-regulates miR-490-3p expression in CRC tissue. Gain- and loss-of-function assays in vitro and in vivo reveal that miR-490-3p suppresses cancer cell proliferation by inducing apoptosis and inhibits cell invasiveness by repressing the initiation of epithelial-to-mesenchymal transition (EMT), a key mechanism in cancer cell invasiveness and metastasis. The frequently rearranged in advanced T-cell lymphomas (FRAT1) protein was identified as a direct target of miR-490-3p and contributes to its tumor-suppressing effects. miR-490-3p appears to have an inhibitory effect on β-catenin expression in nuclear fractions of CRC cells, whereas FRAT1 expression is associated with the accumulation of β-catenin in the nucleus of cells, which could be weakened by transfection with miR-490-3p. Our findings suggest that the miR-490-3p/FRAT1/β-catenin axis is important in CRC progression and provides new insight into the molecular mechanisms underlying CRC. They may help to confirm the pathway driving CRC aggressiveness and serve for the development of a novel miRNA-targeting anticancer therapy. 

Retracted: No

PubPeer comments:
 Fig. 2E, Fig. 5C and Fig. 6A have two sets of WB bands which appear more similar than expected, with the potential manipulation of WB band cropping. ![file] ,