Xiong Yulin, Jia Ming, Yuan Jing, Zhang Changjiang, Zhu Yan, Kuang Xuemei, Lan Lin, Wang Xiaohong
Key Laboratory of Infectious Disease Research, Institute of Infectious Diseases of Chinese PLA, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Mol Med Rep. 2015 Nov;12(5):6738-44. doi: 10.3892/mmr.2015.4278. Epub 2015 Sep 1.
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.
长链非编码RNA(lncRNAs)是一类不编码蛋白质但在多种生物学过程中起重要作用的RNA。在过去几年中,随着高通量测序技术的应用,大量与病毒感染相关的lncRNAs已被鉴定并深入研究,然而,很少有研究探讨lncRNAs与丙型肝炎病毒(HCV)复制之间的关联。先前的研究表明,信号转导和转录激活因子3(STAT3)被丙型肝炎病毒(HCV)激活,进而增加HCV的复制。然而,其详细的分子机制仅被部分理解。在本研究中,使用人类lncRNA聚合酶链反应(PCR)芯片,鉴定出lnc-IGF2-AS、lnc-7SK、lnc-SChLAP1和lnc-SRA1被STAT3上调。此外,在这四种lncRNAs中,只有lnc-IGF2-AS和lnc-7SK参与了HCV复制。转染siRNA lnc-7SK和siRNA lnc-IGF2-AS可部分抑制Huh7细胞中HCV的复制。数据还表明,当转染siRNA lnc-7SK和siRNA lnc-IGF2-AS时,被鉴定与HCV复制相关的磷脂酰肌醇4-磷酸(PI4P)的表达降低。因此,本研究鉴定出两种新型lncRNAs,lnc-IGF2-AS和lnc-7SK,它们可被STAT3上调,并通过调节PI4P参与HCV复制。