MiR-27a as a predictor for the activation of hepatic stellate cells and hepatitis B virus-induced liver cirrhosis.
MiR-27a as a predictor for the activation of hepatic stellate cells and hepatitis B virus-induced liver cirrhosis.
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MiR-27a作为肝星状细胞激活和乙型肝炎病毒诱导的肝硬化的预测因子
DOI：
10.18632/oncotarget.23262
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发表时间：
2018-01-02
期刊：
影响因子：
--
通讯作者：
Su SB
中科院分区：
文献类型：
--
作者：
Zhang H;Yan XL;Guo XX;Shi MJ;Lu YY;Zhou QM;Chen QL;Hu YY;Xu LM;Huang S;Su SB
循环microRNAs （miRNAs）可以作为诊断肝脏和其他疾病的生物标志物。需要无创方法来补充和改进目前筛查肝硬化生物标志物的策略。我们确定了血清mirna水平是否可以区分慢性乙型肝炎（CHB）和慢性乙型肝炎诱导的肝硬化（HBC），并研究了其中的潜在机制。我们发现血清miR-27a在HBC中显著上调，将HBC与CHB和健康对照（Ctrl）区分开来（P<0.0001，曲线下面积（AUC）分别=0.82和0.87）。具体来说，当miR-27a与miR-122联合时，HBC与CHB分化，AUC=0.94。肝失代偿型HBC患者血清miR-27a水平显著高于代偿型HBC患者（P=0.0009）。与盐水处理大鼠相比，dmn诱导的肝硬化大鼠血清中MiR-27a也显著上调（P<0.0001）。此外，miR-27a的下调通过上调α-SMA和COL1A2的表达，通过靶向PPARγ、fox01、APC、P53和RXRα，抑制了miR-27a在活化的肝星状细胞（hsc）中的增殖和过表达。我们的研究表明，循环miR-27a可以作为hsc激活和HBC发生发展的预测因子。
Circulating microRNAs (miRNAs) can be employed as biomarkers to diagnose liver and other diseases. Noninvasive approaches are needed to complement and improve the current strategies for screening for biomarkers liver cirrhosis. We determined whether the serum levels of miRNAs can distinguish between chronic hepatitis B (CHB) and CHB-induced cirrhosis (HBC) and investigated the potential mechanisms involved. We found that serum miR-27a was significantly up-regulated in HBC, distinguishing HBC from CHB and healthy controls (Ctrl) (P<0.0001, the area of under the curve (AUC) =0.82 and 0.87, respectively). Specifically, when miR-27a was combined with miR-122, HBC was differentiated from CHB with an AUC=0.94. The serum miR-27a level in HBC patients with hepatic decompensation was significantly higher than that in patients with compensated HBC (P=0.0009). MiR-27a was also significantly up-regulated in the serum of rats with DMN-induced liver cirrhosis compared to that in saline-treated rats (P<0.0001). Furthermore, the down-regulation of miR-27a inhibited the proliferation and overexpression of miR-27a in activated hepatic stellate cells (HSCs) through the up-regulation of α-SMA and COL1A2 expression by targeting PPARγ, FOXO1, APC, P53 and RXRα. Our study demonstrated that circulating miR-27a can be used as a predictor for the activation of HSCs and the occurrence and development of HBC.
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