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Open Access 01-12-2017 | Research

miR-4775 promotes colorectal cancer invasion and metastasis via the Smad7/TGFβ-mediated epithelial to mesenchymal transition

Authors: Senlin Zhao, Hongcheng Sun, Weiliang Jiang, Yushuai Mi, Dongyuan Zhang, Yugang Wen, Dantong Cheng, Huamei Tang, Shaohan Wu, Yang Yu, Xisheng Liu, Weiyingqi Cui, Meng Zhang, Xiaofeng Sun, Zongguang Zhou, Zhihai Peng, Dongwang Yan

Published in: Molecular Cancer | Issue 1/2017

Abstract

Background

Despite advancements in the diagnosis and treatment of colorectal cancer (CRC), many patients die because of tumor metastasis or recurrence. Therefore, identifying new prognostic markers and elucidating the mechanisms of CRC metastasis and recurrence will help to improve the prognosis of the disease. As dysregulation of microRNAs is strongly related to cancer progression, the aim of this study was to identify the role of miR-4775 in the prognosis of CRC patients and the underling mechanisms involved in CRC progression.

Methods

qPCR and in situ hybridization were used to evaluate the expression of miR-4775 in 544 pairs of paraffin-embedded normal and CRC tissues. Kaplan–Meier analysis with the log-rank test was used for survival analyses. Immunohistochemical staining was applied to investigate the expression of miR-4775-regulated Smad7/TGFβ pathway-associated markers. In vitro and in vivo invasion and metastasis assays were used to explore the function of miR-4775 in the progression of CRC.

Results

miR-4775 was identified as a high-risk factor for CRC metastasis and recurrence, with high levels predicting poor survival among the 544 studied CRC patients. Furthermore, high miR-4775 expression promoted the invasion of CRC cells as well as metastasis and the epithelial to mesenchymal transition (EMT) via Smad7-mediated activation of TGFβ signaling both in vitro and in vivo. Downregulating miR-4775 or overexpressing Smad7 reversed the tumor-promoting roles of miR-4775/Smad7/TGFβ in vitro and in vivo.

Conclusion

miR-4775 promotes CRC metastasis and recurrence in a Smad7/TGFβ signaling-dependent manner, providing a new therapeutic target for inhibiting the metastasis or recurrence of the disease.

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Title: miR-4775 promotes colorectal cancer invasion and metastasis via the Smad7/TGFβ-mediated epithelial to mesenchymal transition
Authors: Senlin Zhao
Hongcheng Sun
Weiliang Jiang
Yushuai Mi
Dongyuan Zhang
Yugang Wen
Dantong Cheng
Huamei Tang
Shaohan Wu
Yang Yu
Xisheng Liu
Weiyingqi Cui
Meng Zhang
Xiaofeng Sun
Zongguang Zhou
Zhihai Peng
Dongwang Yan
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2017
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/s12943-017-0585-z

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