Wang Yu, Lee Alvin T C, Ma Joel Z I, Wang Jingbo, Ren Jianwei, Yang Yuchen, Tantoso Erwin, Li Kuo-Bin, Ooi London L P J, Tan Patrick, Lee Caroline G L
Department of Biochemistry, National University of Singapore, Singapore 119077, Singapore.
J Biol Chem. 2008 May 9;283(19):13205-15. doi: 10.1074/jbc.M707629200. Epub 2008 Mar 4.
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.
与其他癌症一样，异常的基因调控在肝细胞癌（HCC）中具有显著特征。最近发现，微小RNA（miRNA）在转录后/翻译水平调控基因表达。对19例HCC患者的157种miRNA的表达谱进行了检测，发现19种上调和3种下调的miRNA与HCC相关。通过计算机模拟预测了这22种miRNA的潜在基因靶点，这些靶点在34条生物学途径中显著富集，其中大多数在致癌过程中经常失调。对HCC患者中上调最显著的miRNA-224（miR-224）进行进一步研究发现，miR-224可增加凋亡细胞死亡以及细胞增殖，并靶向凋亡抑制因子-5（API-5）抑制API-5转录本表达。值得注意的是，在HCC患者中发现miR-224表达与API-5表达呈负相关（p < 0.05）。因此，我们的研究结果确定了miR-224在体内的真正靶点，并重申了miRNA在细胞过程失调中可能最终导致肿瘤发生的重要作用。
