microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma.
microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma.
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DOI：
10.1038/msb.2010.58
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发表时间：
2010-08-24
影响因子：
9.9
通讯作者：
中科院分区：
文献类型：
--
作者：
肿瘤的发生涉及多步骤的基因改变。为了阐明microRNA(MiRNA)-基因相互作用网络在肿瘤发生中的作用，我们检测了96对肝细胞癌(HCC)肿瘤/非肿瘤组织中miRNA-基因的全基因组表达谱。对miRNAs和mRNAs协同表达的综合分析表明，miR-122在肝细胞癌中低表达，并且miR-122种子匹配基因的表达增加导致线粒体代谢功能的丧失。此外，miR-122次级靶点表达降低，是肝细胞癌良好的预后标志物。来自同一队列中另外180例肝癌和40例肝硬变患者的转录组数据被用来证实miR-122主要和次要靶基因集的反相关性。通过用Anagomir治疗沉默miR-122，然后进行基因表达微阵列分析，可以在小鼠肝脏中概括肝癌的发现。在体外，miR-122数据进一步提供了miR-122控制基因的诱导和线粒体代谢障碍之间的直接联系。总之，miR-122调节线粒体代谢，其缺失可能不利于维持关键的肝功能，并导致肝癌患者的发病率和死亡率。
Tumorigenesis involves multistep genetic alterations. To elucidate the microRNA (miRNA)–gene interaction network in carcinogenesis, we examined their genome-wide expression profiles in 96 pairs of tumor/non-tumor tissues from hepatocellular carcinoma (HCC). Comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-122 is under-expressed in HCC and that increased expression of miR-122 seed-matched genes leads to a loss of mitochondrial metabolic function. Furthermore, the miR-122 secondary targets, which decrease in expression, are good prognostic markers for HCC. Transcriptome profiling data from additional 180 HCC and 40 liver cirrhotic patients in the same cohort were used to confirm the anti-correlation of miR-122 primary and secondary target gene sets. The HCC findings can be recapitulated in mouse liver by silencing miR-122 with antagomir treatment followed by gene-expression microarray analysis. In vitro miR-122 data further provided a direct link between induction of miR-122-controlled genes and impairment of mitochondrial metabolism. In conclusion, miR-122 regulates mitochondrial metabolism and its loss may be detrimental to sustaining critical liver function and contribute to morbidity and mortality of liver cancer patients.
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影响因子：
14.9
作者：
Kanehisa M;Araki M;Goto S;Hattori M;Hirakawa M;Itoh M;Katayama T;Kawashima S;Okuda S;Tokimatsu T;Yamanishi Y
通讯作者：
Yamanishi Y
影响因子：
46.9
作者：
Jackson, AL;Bartz, SR;Linsley, PS
通讯作者：
Linsley, PS
影响因子：
56.9
作者：
Jopling, CL;Yi, MK;Sarnow, P
通讯作者：
Sarnow, P
影响因子：
11.2
作者：
Gramantieri, Laura;Ferracin, Manuela;Negrini, Massimo
通讯作者：
Negrini, Massimo
影响因子：
4
作者：
Kutay, Huban;Bai, Shoumei;Ghoshal, Kalpana
通讯作者：
Ghoshal, Kalpana