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

Molecular Cancer

Research

Weiliang Jiang¹  Zongguang Zhou²  Zhihai Peng³  Dongyuan Zhang³  Yang Yu³  Senlin Zhao³  Hongcheng Sun³  Dantong Cheng³  Yushuai Mi³  Xisheng Liu³  Dongwang Yan³  Yugang Wen³  Shaohan Wu⁴  Xiaofeng Sun⁵  Weiyingqi Cui⁵  Meng Zhang⁶  Huamei Tang⁷ 

[1] Department of Gastroenterology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, 85 Wujin Road, 200080, Shanghai, China;Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang Street, 610041, Chengdu, Sichuan, China;Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, 85 Wujin Road, 200080, Shanghai, China;Department of General Surgery, The Second Affiliated Hospital of Jiaxing College, 1518 Huancheng North Road, 314000, Jiaxing, Zhejiang, China;Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, SE-581 83, Linköping, Sweden;Department of Pathology, Fudan University, Shanghai Cancer Center, 270 Dongan Road, 200030, Shanghai, China;Department of Pathology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, 85 Wujin Road, 200080, Shanghai, China;

关键词: miR-4775;    Smad7;    TGFβ signaling;    Colorectal cancer;    EMT;   

DOI  :  10.1186/s12943-017-0585-z

 received in 2016-08-09, accepted in 2017-01-04,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundDespite 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.MethodsqPCR 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.ResultsmiR-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.ConclusionmiR-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.

【 授权许可】

CC BY   
© The Author(s). 2017