Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.
Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100010, China.
Int J Biol Sci. 2021 Jul 5;17(11):2826-2840. doi: 10.7150/ijbs.59227. eCollection 2021.
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.
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）在内的相关基因失调。已有研究报道，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 的表达呈时间和剂量依赖性上调。功能上，siRNA 介导的 UCA1 敲低上调了干扰素（IFN）反应，从而增加了干扰素刺激基因（ISG）的表达，进而抑制了 HCV 复制。生物信息学分析和实验结果表明，UCA1 作为竞争性内源性 RNA，可以海绵 microRNA（miR）-145-5p，其靶向抑制细胞因子信号转导 7（SOCS7）mRNA，进而介导 SOCS7 沉默。此外，SOCS7 蛋白对 IFN 反应发挥抑制作用，从而促进 HCV 复制。总之，我们的研究结果首次表明，UCA1 可以拮抗 miR-145-5p 的表达，从而上调 SOCS7 的水平，进而抑制 Huh7.5 细胞中的抗病毒反应。
