MicroRNA-581 promotes hepatitis B virus surface antigen expression by targeting Dicer and EDEM1.
MicroRNA-581 promotes hepatitis B virus surface antigen expression by targeting Dicer and EDEM1.
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DOI：
10.1093/carcin/bgu128
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发表时间：
2014-09
期刊：
影响因子：
4.7
通讯作者：
Yu-Qun Wang;Yong-Feng Ren;Yi-Jiang Song;Yong-feng Xue;Xue-Jiao Zhang;Su-Ting Cao;Zhu-jun Deng;Jianmin Wu;Li Chen;Guiling Li;Ke-Qing Shi;Yong-Ping Chen;H. Ren;Ai-long Huang;Kai-Fu Tang
中科院分区：
文献类型：
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作者：
Yu-Qun Wang;Yong-Feng Ren;Yi-Jiang Song;Yong-feng Xue;Xue-Jiao Zhang;Su-Ting Cao;Zhu-jun Deng;Jianmin Wu;Li Chen;Guiling Li;Ke-Qing Shi;Yong-Ping Chen;H. Ren;Ai-long Huang;Kai-Fu Tang
乙型肝炎病毒表面抗原（HBsAg）是肝细胞癌（HCC）的重要危险因子，在肝癌发生过程中下调。在HCC组织中，MicroRNAs （miRNAs）经常被解除调控。然而，HCC中某些mirna的解除调控是否对HBsAg表达有影响尚不清楚。我们在这里发现，microRNA-581 （miR-581）在肝癌发生过程中被解除调控，促进HBsAg的表达。此外，miR-581靶向Dicer和内质网降解增强α -甘露糖苷酶样蛋白1 （EDEM1）并抑制其表达。虽然Dicer不能加工HBV转录物，但Dicer敲低导致HBsAg分泌增加，很可能是由于Dicer加工的7SL RNA片段水平降低。此外，dicer加工的7SL RNA片段部分抑制了miR-581刺激HBsAg表达的能力。此外，我们发现强迫EDEM1表达抑制mir -581介导的HBsAg诱导。最后，将miR-581转染到HepG2.2.15细胞中，促进细胞增殖，导致参与发育、细胞增殖和蛋白分泌的基因上调。总之，我们得出结论，miR-581通过靶向Dicer和EDEM1促进HBsAg表达。我们的研究结果表明，在肝癌发生过程中miR-581的下调可能导致HBsAg表达降低并阻碍HCC的发展。
Hepatitis B virus surface antigen (HBsAg) is an important risk factor for hepatocellular carcinoma (HCC) and is downregulated during hepatocarcinogenesis. MicroRNAs (miRNAs) are frequently deregulated in HCC tissues. However, whether the deregulation of certain miRNAs in HCC has an impact on HBsAg expression remains unclear. We found here that microRNA-581 (miR-581), which is deregulated during hepatocarcinogenesis, promoted HBsAg expression. Additionally, miR-581 targeted Dicer and endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 1 (EDEM1) and repressed their expression. Although Dicer cannot process HBV transcripts, Dicer knockdown led to increased HBsAg secretion, most likely due to a reduction in the levels of Dicer-processed 7SL RNA fragments. Moreover, Dicer-processed 7SL RNA fragments partially inhibited the ability of miR-581 to stimulate HBsAg expression. Furthermore, we found that forced EDEM1 expression inhibited miR-581-mediated induction of HBsAg. Finally, transfection of miR-581 into HepG2.2.15 cells promoted cell proliferation and led to upregulation of genes involved in development, cell proliferation and protein secretion. Altogether, we conclude that miR-581 promotes HBsAg expression by targeting Dicer and EDEM1. Our findings suggest that downregulation of miR-581 during hepatocarcinogenesis may lead to a reduction in HBsAg expression and impede HCC development.