Regulation of the expression of the liver cancer susceptibility gene MICA by microRNAs.

Regulation of the expression of the liver cancer susceptibility gene MICA by microRNAs.
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通过microRNAS调节肝癌易感性基因云母的表达。

DOI:
10.1038/srep02739
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发表时间:
2013
期刊:
影响因子:
4.6
通讯作者:
Koike, Kazuhiko
Koike, Kazuhiko
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kishikawa, Takahiro;Otsuka, Motoyuki;Yoshikawa, Takeshi;Ohno, Motoko;Takata, Akemi;Shibata, Chikako;Kondo, Yuji;Akanuma, Masao;Yoshida, Haruhiko;Koike, Kazuhiko

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肝细胞癌(HCC)是全球公共卫生的威胁。我们以前确定了在MHC I类多肽相关序列A(云母)基因的启动子区的单核苷酸多态性(SNP)与肝炎病毒相关的HCC的风险的关联。由于该SNP影响云母表达水平,因此调节云母表达水平在预防HCC中可能是重要的。我们在此表明,microRNA(miR)25-93- 106 b簇可以调节HCC细胞中的云母水平。miR 25-93- 106 b簇的过表达显著抑制云母表达。相反,沉默该miR簇增强了表达大量云母的细胞中的云母表达。在NKG 2D结合试验和体内细胞杀伤模型中,miR 25 -93- 106 b簇引起的云母表达水平变化具有生物学意义。这些数据表明,云母表达水平的调节miRNA可能是一个有用的方法来调节肝癌在肝炎病毒感染。
Hepatocellular carcinoma (HCC) is a threat to public health worldwide. We previously identified the association of a single nucleotide polymorphism (SNP) at the promoter region of the MHC class I polypeptide-related sequence A (MICA) gene with the risk of hepatitis-virus-related HCC. Because this SNP affects MICA expression levels, regulating MICA expression levels may be important in the prevention of HCC. We herein show that the microRNA (miR) 25-93-106b cluster can modulate MICA levels in HCC cells. Overexpression of the miR 25-93-106b cluster significantly suppressed MICA expression. Conversely, silencing of this miR cluster enhanced MICA expression in cells that express substantial amounts of MICA. The changes in MICA expression levels by the miR25-93-106b cluster were biologically significant in an NKG2D-binding assay and an in vivo cell-killing model. These data suggest that the modulation of MICA expression levels by miRNAs may be a useful method to regulate HCCs during hepatitis viral infection.
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