Down-regulation of Transducin-Like Enhancer of Split protein 4 in hepatocellular carcinoma promotes cell proliferation and epithelial-Mesenchymal-Transition.
Transducin-Like Enhancer of Split protein 4 (TLE4) has been reported to be involved in some subsets of acute myeloid leukemia and colorectal cancer. In the present study, we aimed to explore the role of TLE4 in tumorigenesis and cancer progression in hepatocellular carcinoma (HCC).



The expression pattern of TLE4 in HCC was determined by Western-blot and qRT-PCR, gain-of-function and loss-of-function was used to explore the biological role of TLE4 in HCC cells. A xenograft model was established to confirm its effects on proliferation.



The protein expression levels of TLE4 were significantly down-regulated in HCC tissues compared to matched adjacent normal liver tissues. In vitro, down-regulation of TLE4 in Huh7 or SMMC-7721 promoted cell proliferation and ectopical expression of TLE4 in Hep3B or Bel-7404 suppressed cell proliferation. In addition, the cell colony formation ability was enhanced after down-regulation of TLE4 expression in Huh-7 but suppressed after over-expression in Hep3B. Furthermore, down-regulation of TLE4 increased the cell invasion ability, as well as increased the expression level of Vimentin and decreased that of E-cadherin, indicating a phenotype of epithelial-mesenchymal transition (EMT) in HCC cells. On the contrary, ectopical expression of TLE4 in HCC cells decreased the cell invasion ability and inhibited EMT. In vivo, compared to control group, xenograft tumor volumes were significantly decreased in TLE4 overexpression group.



These results demonstrated that TLE4 might play important regulatory roles in cellular proliferation and EMT process in HCC.
Department of Hepatic Surgery, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
Xiao-Cai
XC
Wu
Department of Hepatic Surgery, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
Cui-Cui
CC
Xiao
Department of Hepatic Surgery, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
Hua
H
Li
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
Yan
Y
Tai
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
Qi
Q
Zhang
Department of Hepatic Surgery, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address: yysysu2@163.com.
Yang
Y
Yang
D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D009687:Nuclear Proteins; D012097:Repressor Proteins; C465817:TLE4 protein, human
Cell proliferation; Epithelial-mesenchymal-transition; Hepatocellular carcinoma; Transducin like enhancer protein 4; Tumor invasion