Modulation of miR-122 expression affects the interferon response in human hepatoma cells
Modulation of miR-122 expression affects the interferon response in human hepatoma cells
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miR-122表达的调节影响人肝癌细胞的干扰素反应
DOI：
10.3892/mmr.2012.1233
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发表时间：
2013-02-01
影响因子：
3.4
通讯作者：
Zhang, Fengmin
中科院分区：
文献类型：
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作者：
Li, Aimei;Qian, Jun;Zhang, Fengmin
I型干扰素被认为在限制肿瘤生长方面发挥着重要作用。研究表明，诱导内源性干扰素的表达是干扰素治疗成功的关键机制之一。然而，最近的研究表明，I型干扰素治疗在某些肿瘤的临床治疗中存在局限性，包括肝细胞癌(HCC)。已有研究表明，miR-122在肝细胞癌中的表达明显降低，恢复miR-122的表达可能改善该病的预后。此前的研究还表明，肝脏miR-122水平较低的患者对干扰素治疗的反应较差。我们先前发现，当miR-122在人少突胶质细胞中被抑制时，干扰素的表达降低。基于这些研究，推测miR-122的表达可能调节内源性干扰素的表达，从而影响干扰素治疗肝细胞癌的疗效。本研究的结果表明，当外源干扰素处理时，miR-122丰富的Huh7细胞比miR-122缺乏的HepG2细胞的反应更显着。上调miR-122显著增强外源性干扰素诱导的干扰素表达能力，而下调miR-122则降低这一能力。这些数据表明，miR-122的高水平表达可能促进外源性干扰素诱导的I型干扰素的表达，从而有助于干扰素的治疗。
Type I interferon (IFN) is believed to play significant roles in limiting tumor growth. It has been revealed that the induction of endogenous IFN expression is one of the key mechanisms for successful IFN therapy. However, recent studies have shown that the efficacy of type I IFN therapy has limitations in the clinical treatment of certain tumors, including hepatocellular carcinoma (HCC). It has been revealed that the expression of miR-122 is significantly decreased in HCC and that restoration of miR-122 expression may improve the prognosis of this condition. Previous studies also showed that patients with low miR-122 levels in the,liver responded poorly to the IFN therapy. We previously identified that the IFN expression was reduced when miR-122 was suppressed in human oligodendrocytes. Based on these studies, it was hypothesized that the expression of miR-122 may modulate the endogenous IFN expression and subsequently affect the treatment outcome of IFN therapy for HCC. The results of the present study showed that miR-122-abundant Huh7 cells responded more significantly than miR-122-deficient HepG2 cells when treated with exogenous IFN. Upregulation of miR-122 significantly increased the ability of exogenous IFN-induced IFN expression, while downregulation of miR-122 decreased this ability. These data indicate that a high level of miR-122 expression may promote the expression of type I IFN induced by exogenous IFNs and further contribute to IFN therapy for HCC.