Research Papers:

Down-regulation of Krüppel-like factor-4 by microRNA-135a-5p promotes proliferation and metastasis in hepatocellular carcinoma by transforming growth factor-β1

Shanshan Yao _, Chuan Tian, Youcheng Ding, Qingwang Ye, Yong Gao, Ning Yang and Qi Li

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Oncotarget. 2016; 7:42566-42578. https://doi.org/10.18632/oncotarget.9934

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Shanshan Yao1,*, Chuan Tian1,*, Youcheng Ding2, Qingwang Ye3, Yong Gao1, Ning Yang3, Qi Li1,4

1Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120,China

2Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120,China

3Department of Liver Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China

4Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China

*These authors have contributed equally to this work

Correspondence to:

Qi Li, email: Leeqi2001@hotmail.com

Ning Yang, email: Lancet00@163.com

Keywords: KLF4, miR-135a-5p, TGF-β1, hepatocellular carcinoma

Received: October 17, 2015    Accepted: May 11, 2016    Published: June 10, 2016


Krüppel-like Factor-4 (KLF4) is a zinc finger transcription factor which plays an important role in cell cycle, proliferation and apoptosis. In Hepatocellular Carcinoma (HCC), the function of KLF4 has been characterized as tumor suppressor. However, the mechanism remains largely unknown. In this study, we demonstrated that TGF-β1 down-regulated KLF4 by activating miR-135a-5p. MiR-135a-5p promoted proliferation and metastasis in HCC cells by direct targeting KLF4 both in vitro and in vivo. In addition, miR-135a-5p expression was up-regulated in clinical HCC tissues, and was inversely correlated with the expression of KLF4. Taken together, our data indicated that TGF-β1 down-regulated KLF4 by activating miR-135a-5p, promoting proliferation and metastasis in HCC.

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