Li Yan, Wu Rina, Liu Zhongrong, Fan Jianyong, Yang Huilan
Southern Medical University, Guangzhou, Guangdong 510515, P.R. China ; Department of Dermatology, Affiliated Hospital of Inner Mongolia Medical University, Hohehot, Inner Mongolia 010050, P.R. China.
Department of Dermatology, Affiliated Hospital of Inner Mongolia Medical University, Hohehot, Inner Mongolia 010050, P.R. China.
Exp Ther Med. 2014 May;7(5):1291-1296. doi: 10.3892/etm.2014.1588. Epub 2014 Feb 26.
Varicella-zoster virus (VZV) causes chronic pain and serious complications, including zoster paresis. However, the mechanism of VZV replication, a critical part of VZV pathogenesis, remains largely unknown and was investigated in the present study. The upregulation of microRNA-21 (miR-21) was identified following VZV infection by quantitative polymerase chain reaction. The hypothesis that the overexpression of miR-21 activates the signal transducer and activator of transcription 3 (STAT3) signaling pathway was validated by measuring the mRNA expression levels of STAT3 and the anti-apoptotic protein survivin in human malignant melanoma (MeWo) and human embryonic lung fibroblast (HELF) cell lines transfected with miR-21-mimic and comparing them with those in cells transfected with miR-control. To further study the interaction of miR-21, STAT3 and VZV replication, the effects of miR-21 overexpression and STAT3 knockdown were evaluated. Higher virus titers were detected when miR-21 was upregulated . Moreover, it was identified that significantly lower virus titers were present in MeWo cells in which STAT3 was knocked down. In addition, the overexpression of miR-21 did not stimulate VZV replication in the MeWo cell line when the STAT3 gene was silenced. Therefore, the observations of the present study indicate that the enforced expression of miR-21 promotes the replication of VZV by activating STAT3 .
水痘带状疱疹病毒（VZV）可引发慢性疼痛和严重并发症，包括带状疱疹性轻瘫。然而，VZV复制机制作为VZV发病机制的关键部分，在很大程度上仍不清楚，本研究对此进行了探究。通过定量聚合酶链反应，在VZV感染后发现了微小RNA-21（miR-21）的上调。通过测量转染了miR-21模拟物的人恶性黑色素瘤（MeWo）细胞系和人胚肺成纤维细胞（HELF）细胞系中信号转导子和转录激活子3（STAT3）的mRNA表达水平，并与转染了miR-对照的细胞进行比较，验证了miR-21过表达激活STAT3信号通路的假说。为了进一步研究miR-21、STAT3与VZV复制之间的相互作用，评估了miR-21过表达和STAT3敲低的影响。当miR-21上调时，检测到更高的病毒滴度。此外，还发现STAT3被敲低的MeWo细胞中病毒滴度显著降低。此外，当STAT3基因沉默时，miR-21的过表达并未刺激MeWo细胞系中的VZV复制。因此，本研究的观察结果表明，miR-21的强制表达通过激活STAT3促进VZV的复制。
