MiR-483-5p promotes IGF-II transcription and is associated with poor prognosis of hepatocellular carcinoma.
MiR-483-5p promotes IGF-II transcription and is associated with poor prognosis of hepatocellular carcinoma.
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MiR-483-5p促进IGF-II转录并与肝细胞癌不良预后相关
DOI：
10.18632/oncotarget.21737
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发表时间：
2017-11-21
期刊：
影响因子：
--
通讯作者：
Huang J
中科院分区：
文献类型：
--
作者：
Tang S;Chen Y;Feng S;Yi T;Liu X;Li Q;Liu Z;Zhu C;Hu J;Yu X;Wang M;Cao G;Tang H;Bie C;Ma F;Tang H;Du G;Huang J
人胰岛素样生长因子-II(IGF-II)基因转录四个mRNAs(P1mRNAP4mRNAs)，P3mRNAs过表达与肝癌的发生有关。IGF-II衍生的miR-483-5p与癌症的发生有关。在此，我们研究了miR-483-5p在P3mRNA过表达调控中的作用及其在肝细胞癌中的作用。我们的结果表明miR-483-5p通过靶向P3mRNA的5‘非翻译区(5’UTR)在肝细胞癌中上调P3mRNA的转录。其作用机制是通过miR-483-5p，使IGF-II基因的P3mRNA5‘非编码区和P3启动子上的Ago1-Ago2复合体与IGF-II基因的P3启动子结合，同时在P3启动子上激活组蛋白标志物组蛋白3赖氨酸4三甲基化(H3K4me3)、组蛋白3赖氨酸27乙酰化(H3K27ac)和组蛋白4赖氨酸5/8/12/16乙酰化(H4Kac)。MiR-483-5p的高表达是肝癌患者较短生存期的独立预测因素。提示miR-483-5p通过将Ago1-Ago2复合体募集到P3mRNA5‘端，促进P3mRNA5’端转录，与肝细胞癌预后不良有关。我们的结果为miRNAs上调基因表达提供了一个潜在的新模型。
The human insulin-like growth factor-II (IGF-II) gene transcribes four mRNAs (P1 mRNA-P4 mRNA), and P3 mRNA overexpression contributes to hepatocarcinogenesis. IGF-II-derived miR-483-5p is implicated in the development of cancers. Here, we investigated the involvement of miR-483-5p in P3 mRNA overexpression regulation and its role in hepatocellular carcinoma. Our results showed that miR-483-5p up-regulated P3 mRNA transcription by targeting the 5′-untranslated region (5′UTR) of P3 mRNA in hepatocellular carcinoma. The mechanism was involved in recruiting of an argonaute 1(Ago1)-argonaute 2 (Ago2) complex to the P3 mRNA 5′UTR and the P3 promoter of IGF-II gene by miR-483-5p, accompanied by increased enrichment of RNA polymerase II and activating histone marks histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 27 acetylation (H3K27ac), and histone 4 lysine 5/8/12/16 acetylation (H4Kac) at the P3 promoter. High miR-483-5p expression was an independent predictor for shorter survival of HCC patients. The findings suggest that miR-483-5p promotes P3 mRNA transcription by recruiting the Ago1-Ago2 complex to the P3 mRNA 5′UTR and is associated with poor prognosis of HCC. Our results display a potential new model for miRNAs to up-regulate gene expression.
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影响因子：
3.7
作者：
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作者：
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Li LC
DOI：
10.1073/pnas.0808830105
发表时间：
2008-10-21
影响因子：
11.1
作者：
Kim, Daniel H.;Saetrom, Pal;Rossi, John J.
通讯作者：
Rossi, John J.