The role of microRNA expression pattern in human intrahepatic cholangiocarcinoma
The role of microRNA expression pattern in human intrahepatic cholangiocarcinoma
复制标题
microRNA表达模式在人肝内胆管癌中的作用。
DOI：
10.1016/j.jhep.2008.09.015
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发表时间：
2009-02-01
影响因子：
25.7
通讯作者：
Wang, Hong-Yang
中科院分区：
文献类型：
--
作者：
Chen, Lei;Yan, He-Xin;Wang, Hong-Yang
背景/目的：MicroRNAs是一个小的非编码基因家族，以转录后方式参与基因表达调控，参与细胞增殖、分化和凋亡。我们的目的是鉴别人类肝内胆管癌中统计学上独特的miRNA谱，以用于诊断，并研究它们在胆管癌中各种细胞生物学过程中的特异性参与。方法：采用激光捕获显微解剖技术和成熟miRNA TaqMan检测技术，对27例人ICCs、10例正常胆管细胞和8例正常肝组织中miRNA的全基因组表达进行精确定量评估。将两个选定的mirna mir-204和mir-320分别引入胆管癌细胞系，研究它们对潜在靶基因Bcl-2和Mcl-1的影响。结果：肿瘤组织和正常组织有38个microrna簇可明显区分。至少有两组不同的肿瘤样本与碳水化合物抗原19-9的高或低表达水平相关。此外，外源表达mir-320或mir-204可负调控Mcl-1或Bcl-2的表达，促进化疗药物引发的细胞凋亡。结论：miRNA表达谱与ICC的生物学和临床行为密切相关。调节异常表达的mirna可能是一种很有前途的治疗策略。(C) 2008年欧洲肝脏研究协会。Elsevier B.V.版权所有。
Background/Aims: MicroRNAs are a small non-coding family of genes involved in the regulation of gene expression in a post-transcriptional manner and contribute to cell proliferation, differentiation and apoptosis. Our aims were to identify statistically unique miRNA profiles in human intrahepatic cholangiocarcinoma for diagnosis and investigate their specific involvement in various cell biological processes in cholangiocarcinoma. Methods: Laser capture microdissection techniques and TaqMan miRNA assays for mature miRNAs were performed to assess the genomewide expression of miRNAs in 27 human ICCs, 10 normal cholangiocyte cells and 8 normal liver tissues precisely and quantitatively. Two selected miRNAs, mir-204 and mir-320, were introduced into cholangiocarcinoma cell lines to examine their effects on potential target genes, Bcl-2 and Mcl-1, respectively. Results: A cluster of 38 miRNAs was markedly distinguishable between tumor and normal tissues. At least two distinct clusters of tumor samples could be identified that were associated with the higher or lower expression levels of carbohydrate antigen 19-9. Moreover, the exogenous expression of mir-320 or mir-204 could negatively regulate Mcl-1 or Bcl-2 expression and facilitate chemotherapeutic drug-triggered apoptosis. Conclusions:miRNA expression profiles are closely associated with the biological and clinical behavior of ICC. The modulation of aberrantly expressed miRNAs might prove a promising therapeutic strategy. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.