STAT3-regulated long non-coding RNAs lnc-7SK and lnc-IGF2-AS promote hepatitis C virus replication

Abstract

Long non-coding RNAs (lncRNAs) are a class of RNAs that do not code protein but are important in diverse biological processes. In previous years, with the application of high-throughput sequencing, a large number of lncRNAs associated with virus infections have been identified and intensively investigated, however, there are few studies examining the association between lncRNAs and HCV replication. Previous studies have demonstrated that signal transducer and activator of transcription 3 (STAT3) is activated by the hepatitis C virus (HCV) and in turn increases the replication of HCV. However, the detailed molecular mechanism is only partially understood. In the present study, using human lncRNA polymerase chain reaction (PCR) arrays, it was identified that lnc-IGF2-AS, lnc-7SK, lnc-SChLAP1 and lnc-SRA1 are upregulated by STAT3. In addition, among these four lncRNAs, only lnc-IGF2-AS and lnc-7SK were involved in HCV replication. Transfection of siRNA lnc-7SK and siRNA lnc-IGF2-AS partially inhibited the replication of HCV in Huh7 cells. Data also indicated that when transfected with siRNA lnc-7SK and siRNA lnc-IGF2-AS, the expression of phosphatidylinositol 4-phosphate (PI4P), which was identified to be associated with HCV replication, was reduced. Thus, the present study identified two new types of lncRNAs, lnc-IGF2-AS and lnc-7SK, which can be upregulated by STAT3 and are involved in HCV replication by regulating PI4P.