Downregulation of miR-122 in the rodent and human hepatocellular carcinomas
Downregulation of miR-122 in the rodent and human hepatocellular carcinomas
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DOI：
10.1002/jcb.20982
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发表时间：
2006-10-15
影响因子：
4
通讯作者：
Ghoshal, Kalpana
中科院分区：
文献类型：
--
作者：
Kutay, Huban;Bai, Shoumei;Ghoshal, Kalpana
MicroRNAs(MiRs)是一种保守的非编码小RNA，负向调节基因表达。MiR谱在癌症中明显改变，其中一些在肿瘤发生中起到了因果作用。在这里，我们报告了在喂饲叶酸、蛋氨酸和胆碱缺乏(FMD)饮食的雄性Fisher大鼠发生的肝细胞癌(HC)中miR表达谱的变化。通过微阵列分析对miR图谱的比较表明，与年龄匹配的正常饮食大鼠的肝脏相比，一些miR在肝癌中的表达发生了变化。当let-7a、miR-21、miR-23、miR-130、miR-190和miR-17-92家族基因上调时，丰富的肝脏特异性miR基因miR-122在肿瘤中表达下调。肝脏miR-122的降低是一种肿瘤特异性事件，因为在缺乏饮食的36周后切换到叶酸和甲基充足饮食的大鼠中没有发生这种下降，这不会导致肝癌的发生。在移植的大鼠肝癌中，MIR-122也是沉默的。对人类原发肝癌的外推研究显示，与配对匹配的对照组织相比，20例肿瘤中有10例miR-122的表达显著降低(P=0.013)。这些发现表明miR-122的下调与肝癌的发生有关，并可能成为肝癌的潜在生物标志物。
MicroRNAs (miRs) are conserved small non-coding RNAs that negatively regulate gene expression. The miR profiles are markedly altered in cancers and some of them have a causal role in tumorigenesis. Here, we report changes in miR expression profile in hepatocellular carcinomas (HCCs) developed in male Fisher rats-fed folic acid, methionine, and choline-deficient (FMD) diet. Comparison of the miR profile by microarray analysis showed altered expression of some miRs in hepatomas compared to the livers from age-matched rats on the normal diet. While let-7a, miR-21, miR-23, miR-130, miR-190, and miR-17-92 family of genes was upregulated, miR-122, an abundant liver-specific miR, was downregulated in the tumors. The decrease in hepatic miR-122 was a tumor-specific event because it did not occur in the rats switched to the folate and methyl-adequate diet after 36 weeks on deficient diet, which did not lead to hepatocarcinogenesis. miR-122 was also silent in a transplanted rat hepatoma. Extrapolation of this study to human primary HCCs revealed that miR-122 expression was significantly (P = 0.013) reduced in 10 out of 20 tumors compared to the pair-matched control tissues. These findings suggest that the downregulation of miR-122 is associated with hepatocarcinogenesis and could be a potential biomarker for liver cancers.