The regulation of miR-122 which is involved in Hepatitis C virus replication and interferon treatment response

miR-122参与丙型肝炎病毒复制和干扰素治疗反应的调节

• 批准号: 23790774
• 负责人: MUROYAMA Ryosuke
• 金额: $ 2.66万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790774/
• 关键词: microRNA; 発現調節

Mir-122 is a highly abundant and liver-specific miRNA, and reported to enhance Hepatitis C virus (HCV) replication and be associated with interferon treatment response and hepatocarcinogenesis. In this study, we investigated the regulation mechanism of miR-122. At first, we examined the correlation between the expression level of miR-122 and pri-miR-122 which was primary transcript of miR-122 in various hepatoma cell lines by realtime PCR. The result showed the positive correlation between miR-122 and pri-miR-122. Therefore, the expression level of pri-miR-122 was considered to be a major factor which determined that of miR-122. Next, we performed reporter gene assays integrated with truncation in the pri-miR-122 promoter, and determined the region which had high trans-activation effect. Next, we examined the DNA methylation status in the promoter region of pri-miR-122 by sodium bisulfite DNA sequencing, and found that the promoter region of pri-miR-122 was hyper-methylated in the hepatoma cell lines which have the low expression level of pri-miR-122. Moreover, with 5-aza-CdR treatment, the expression level of pri-miR-122 was increased in such cell lines. Therefore, the epigenetic regulation might play an important role in the expression of miR-122.

Mir-122是一种高丰度的肝脏特异性miRNA，可增强丙型肝炎病毒（HCV）的复制，并与干扰素治疗反应和肝癌发生有关。本研究探讨了miR-122的调控机制。首先，我们通过实时荧光PCR检测了miR-122在各种肝癌细胞系中的表达水平与miR-122的初级转录物pri-miR-122之间的相关性。结果显示miR-122和pri-miR-122之间存在正相关性。因此，认为pri-miR-122的表达水平是决定miR-122表达水平的主要因素。接下来，我们在pri-miR-122启动子中进行了整合截短的报告基因测定，并确定了具有高反式激活效应的区域。接下来，我们通过亚硫酸氢钠DNA测序检测了pri-miR-122启动子区域的DNA甲基化状态，发现在pri-miR-122低表达水平的肝癌细胞系中，pri-miR-122的启动子区域高甲基化。此外，用5-aza-CdR处理，pri-miR-122的表达水平在这些细胞系中增加。因此，表观遗传调控可能在miR-122的表达中起重要作用。

项目成果

C 型肝炎の病態と治療効果を規定する miR122 の発現調節機構の解明。

阐明miR122的表达调控机制，决定丙型肝炎的病理和治疗效果。

• 发表时间: 2011
• 作者: 室山良介;後藤覚;Li Wenwen;古渡礼恵;加藤直也
• 通讯作者: 加藤直也

C型肝炎の病態と治療効果を規定するmiR122の発現調節機構の解明

阐明决定丙型肝炎病理和治疗效果的miR122表达调控机制

• 发表时间: 2011
• 作者: 室山良介;後藤覚;Li Wenwen;古渡礼恵;加藤直也;室山良介
• 通讯作者: 室山良介