Down-regulation of Krüppel-like factor-4 by microRNA-135a-5p promotes proliferation and metastasis in hepatocellular carcinoma by transforming growth factor-β1.
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.
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120,China.
Shanshan
S
Yao
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120,China.
Chuan
C
Tian
Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120,China.
Youcheng
Y
Ding
Department of Liver Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
Qingwang
Q
Ye
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120,China.
Yong
Y
Gao
Department of Liver Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
Ning
N
Yang
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120,China.|Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
Qi
Q
Li
D000818:Animals; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D016335:Zinc Fingers
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C544965:MIRN135 microRNA, human; D035683:MicroRNAs; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
KLF4; TGF-β1; hepatocellular carcinoma; miR-135a-5p