Int J Biol Sci 2021; 17(11):2826-2840. doi:10.7150/ijbs.59227 This issue
Long noncoding RNA UCA1 regulates HCV replication and antiviral response via miR-145-5p/SOCS7/IFN pathway
1. Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.
2. Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100010, China.
3. Department of Infectious Disease, the Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, China.
4. Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Zeng H, Li L, Gao Y, Wu G, Hou Z, Liu S. Long noncoding RNA UCA1 regulates HCV replication and antiviral response via miR-145-5p/SOCS7/IFN pathway. Int J Biol Sci 2021; 17(11):2826-2840. doi:10.7150/ijbs.59227. Available from https://www.ijbs.com/v17p2826.htm
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.
Keywords: Hepatitis C virus, urothelial carcinoma-associated 1, microRNA, suppressor of cytokine signaling 7, antiviral response