Suppression of epithelial-mesenchymal transition in hepatocellular carcinoma cells by Krüppel-like factor 4.
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.
Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.|Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai 200120, China.
Qi
Q
Li
Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Weifeng
W
Song
Department of Interventional Radiology, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, China.
Weiyu
W
Wang
Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai 200120, China.
Shanshan
S
Yao
Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai 200120, China.
Chuan
C
Tian
Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Xun
X
Cai
Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Liwei
L
Wang
D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*
C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors
Krüppel-like factor 4; epithelial-mesenchymal transition; hepatocellular carcinoma; microRNA