Suppression of epithelial-mesenchymal transition in hepatocellular carcinoma cells by Krüppel-like factor 4
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Qi Li1,2,*, Weifeng Song1,*, Weiyu Wang3,*, Shanshan Yao2, Chuan Tian2, Xun Cai1, Liwei Wang1
1Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
2Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai 200120, China
3Department of Interventional Radiology, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, China
*These authors have contributed equally to this work
Keywords: Krüppel-like factor 4, epithelial-mesenchymal transition, hepatocellular carcinoma, microRNA
Received: February 25, 2016 Accepted: March 29, 2016 Published: April 18, 2016
Hepatocellular carcinoma (HCC) is one of the most malignant and lethal human cancers. Epithelial-mesenchymal transition (EMT) enhances the carcinogenesis of HCC, and therapies targeting EMT appear to be promising treatments. We have previously shown that Krüppel-like factor 4 (KLF4) suppressed EMT of HCC cells through downregulating EMT-associated proteins. Here, we examined the roles of microRNAs (miRNAs) in KLF4-regulated EMT in HCC cells. KLF4 induced expression of 3 miRNAs (miR-153, miR-506 and miR-200b) that targeted 3′-UTR of Snail1, Slug and ZEB1 mRNAs, respectively, to inhibit protein translation in HCC cells, which was confirmed by promoter luciferase assay. Expression of either miRNA significantly inhibited HCC cell growth and invasiveness, while the effect of combined expression of all 3 miRNAs was more pronounced. Furthermore, overexpression of antisense of all 3 miRNAs abolished the inhibitory effect of KLF4 on HCC cell growth and invasiveness. Together, our data suggest that KLF4 inhibits EMT-enhanced HCC growth and invasion, possibly through reducing EMT-related proteins Snail1, Slug and ZEB1 via increasing miR-153, miR-506 and miR-200b.
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