Upregulation of miR-23a approximately 27a approximately 24 decreases transforming growth factor-beta-induced tumor-suppressive activities in human hepatocellular carcinoma cells.
Transforming growth factor-beta (TGF-beta) plays a dual and complex role in human cancer. In this report, we observe a specific set of MicroRNAs (miRNAs) changed in response to TGF-beta in human hepatocellular carcinoma (HCC) cells by miRNA microarray screening. A cluster of miRNA, miR-23a approximately 27a approximately 24, is induced in an early stage by TGF-beta in Huh-7 cells. Knockdown of Smad4, Smad2 or Smad3 expression by RNA interference can attenuate the response of miR-23a approximately 27a approximately 24 to TGF-beta addition, indicating that this induction is dependent on Smad pathway. We also explore that miR-23a approximately 27a approximately 24 can function as an antiapoptotic and proliferation-promoting factor in liver cancer cells. In addition, expression of this miRNA cluster is found to be remarkably upregulated in HCC tissues versus normal liver tissues. These findings suggest a novel, alternative mechanism through which TGF-beta could induce specific miRNA expression to escape from tumor-suppressive response in HCC cells.
Huang
Shenglin
S
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Medical School of Shanghai Jiaotong University, Shanghai, China.
He
Xianghuo
X
Ding
Jie
J
Liang
Linhui
L
Zhao
Yingjun
Y
Zhang
Zhenfeng
Z
Yao
Xiao
X
Pan
Zhimei
Z
Zhang
Pingping
P
Li
Jinjun
J
Wan
Dafang
D
Gu
Jianren
J
D017209:Apoptosis / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D051785:Smad Proteins / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D035683:MicroRNAs; D051785:Smad Proteins; D016212:Transforming Growth Factor beta