FCCC LOGO Faculty Publications
Cheng D , Zhao S , Tang H , Zhang D , Sun H , Yu F , Jiang W , Yue B , Wang J , Zhang M , Yu Y , Liu X , Sun X , Zhou Z , Qin X , Zhang X , Yan D , Wen Y , Peng Z
MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4
Oncotarget. 2016 Jul 19;7(29) :45199-45213
PMID: 27286257    PMCID: PMC5216716   
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Abstract
BACKGROUND: Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. RESULTS: miR-20a-5p negatively regulated Smad4 by directly targeting its 3'UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients' clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. METHODS: Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan-Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. CONCLUSIONS: miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.
Notes
1949-2553 Cheng, Dantong Zhao, Senlin Tang, Huamei Zhang, Dongyuan Sun, Hongcheng Yu, Fudong Jiang, Weiliang Yue, Ben Wang, Jingtao Zhang, Meng Yu, Yang Liu, Xisheng Sun, Xiaofeng Zhou, Zongguang Qin, Xuebin Zhang, Xin Yan, Dongwang Wen, Yugang Peng, Zhihai P30 CA006927/CA/NCI NIH HHS/United States P30 MH092177/MH/NIMH NIH HHS/United States R01 CA166144/CA/NCI NIH HHS/United States Journal Article United States Oncotarget. 2016 Jul 19;7(29):45199-45213. doi: 10.18632/oncotarget.9900.