Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up-regulation and apoptosis inhibitor-5 as a microRNA-224-specific target.
Like other cancers, aberrant gene regulation features significantly in hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) were recently found to regulate gene expression at the post-transcriptional/translational levels. The expression profiles of 157 miRNAs were examined in 19 HCC patients, and 19 up-regulated and 3 down-regulated miRNAs were found to be associated with HCC. Putative gene targets of these 22 miRNAs were predicted in silico and were significantly enriched in 34 biological pathways, most of which are frequently dysregulated during carcinogenesis. Further characterization of microRNA-224 (miR-224), the most significantly up-regulated miRNA in HCC patients, revealed that miR-224 increases apoptotic cell death as well as proliferation and targets apoptosis inhibitor-5 (API-5) to inhibit API-5 transcript expression. Significantly, miR-224 expression was found to be inversely correlated with API-5 expression in HCC patients (p < 0.05). Hence, our findings define a true in vivo target of miR-224 and reaffirm the important role of miRNAs in the dysregulation of cellular processes that may ultimately lead to tumorigenesis.
Wang
Yu
Y
Department of Biochemistry, National University of Singapore, Singapore 119077, Singapore.
Lee
Alvin T C
AT
Ma
Joel Z I
JZ
Wang
Jingbo
J
Ren
Jianwei
J
Yang
Yuchen
Y
Tantoso
Erwin
E
Li
Kuo-Bin
KB
Ooi
London L P J
LL
Tan
Patrick
P
Lee
Caroline G L
CG
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D013379:Substrate Specificity; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics*
C108386:API5 protein, human; D051017:Apoptosis Regulatory Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins