Hepatitis C virus (HCV) infection involves a variety of viral and host factors, which leads to the dysregulation of number of relevant genes including long noncoding RNAs (LncRNAs). LncRNA urothelial carcinoma-associated 1 (UCA1) has been reported to be upregulated in HCV-infected individuals. In a bid to elucidate on the contribution of UCA1 on HCV replication, we infected Huh7.5 cells with cell culture-derived HCV and found that UCA1 expression was elevated in time- and dose-dependent manners. Functionally, UCA1 knockdown by siRNA upregulated interferon (IFN) responses, thereby increasing the expression of interferon-stimulating genes (ISGs), and subsequently suppressing HCV replication. Bioinformatics analysis and experimental results indicated that, functioning as competitive endogenous RNA, UCA1 could sponge microRNA (miR)-145-5p, which targeted suppressor of cytokine signaling 7 (SOCS7) mRNA and subsequently mediated SOCS7 silencing. Moreover, SOCS7 protein exerted an inhibitory effect on IFN responses, thereby facilitating HCV replication. Taken together, at first, our findings demonstrate that UCA1 can counteract the expression of miR-145-5p, thereby upregulating the level of SOCS7, and in turn leading to the suppression of antiviral response in Huh7.5 cells.

中文翻译：

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长链非编码 RNA UCA1 通过 miR-145-5p/SOCS7/IFN 通路调节 HCV 复制和抗病毒反应

丙型肝炎病毒 (HCV) 感染涉及多种病毒和宿主因素，导致包括长链非编码 RNA (LncRNA) 在内的许多相关基因的失调。据报道，LncRNA 尿路上皮癌相关 1 (UCA1) 在 HCV 感染个体中上调。为了阐明 UCA1 对 HCV 复制的贡献，我们用细胞培养衍生的 HCV 感染 Huh7.5 细胞，发现 UCA1 表达以时间和剂量依赖性方式升高。在功能上，siRNA 敲低 UCA1 上调干扰素 (IFN) 反应，从而增加干扰素刺激基因 (ISG) 的表达，随后抑制 HCV 复制。生物信息学分析和实验结果表明，作为竞争性内源性RNA，UCA1可以海绵microRNA (miR)-145-5p，它靶向抑制细胞因子信号 7 (SOCS7) mRNA 并随后介导 SOCS7 沉默。此外，SOCS7 蛋白对 IFN 反应具有抑制作用，从而促进 HCV 复制。总之，首先，我们的研究结果表明，UCA1 可以抵消 miR-145-5p 的表达，从而上调 SOCS7 的水平，进而抑制 Huh7.5 细胞的抗病毒反应。