MOE&MOH Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Department of Special Medicine, Qingdao University, Qingdao 266071, Shandong, China.
Sci Rep. 2017 Mar 17;7:44705. doi: 10.1038/srep44705.
Glioblastoma (GBM) is the most prevalent and lethal type of primary malignant brain tumour. Recent studies suggest that the discovery of human cytomegalovirus (HCMV)-encoded microRNAs (miRNAs) might play a role in the pathogenesis of diseases, including GBM. In this study, we aimed to analyse the expression and function of HCMV-encoded miRNAs in GBM. We found that miR-UL112-3p expression was significantly elevated in GBM, and its expression levels were highly associated with glioma size, differentiation, WHO stage and the overall and disease-free survival of patients. The overexpression of miR-UL112-3p in the GBM cells promoted cell proliferation, clone formation, migration and invasion. In contrast, the down-regulation of miR-UL112-3p exerted an inverse effects. Tumour suppressor candidate 3 (TUSC3), a potential target gene of miR-UL112-3p, was inversely correlated with miR-UL112-3p expression in GBM tissues and cell lines. Furthermore, we demonstrated that TUSC3 was directly regulated by miR-UL112-3p, and the ectopic expression of TUSC3 reversed the effects of miR-UL112-3p on GBM progression via the AKT signalling pathway. Taken together, these findings collectively demonstrate that miR-UL112-3p exerts its oncogene function by directly targeting TUSC3 in GBM, indicating a potential novel therapeutic target for GBM.
胶质母细胞瘤(GBM)是最常见和最致命的原发性恶性脑肿瘤。最近的研究表明,人类巨细胞病毒(HCMV)编码的 microRNAs(miRNAs)的发现可能在疾病的发病机制中发挥作用,包括 GBM。在这项研究中,我们旨在分析 HCMV 编码的 miRNAs 在 GBM 中的表达和功能。我们发现 miR-UL112-3p 在 GBM 中表达显著上调,其表达水平与胶质瘤大小、分化、WHO 分期以及患者的总生存期和无病生存期高度相关。GBM 细胞中 miR-UL112-3p 的过表达促进了细胞增殖、克隆形成、迁移和侵袭。相反,下调 miR-UL112-3p 则产生相反的效果。肿瘤抑制候选基因 3(TUSC3)是 miR-UL112-3p 的一个潜在靶基因,在 GBM 组织和细胞系中与 miR-UL112-3p 的表达呈负相关。此外,我们证明 TUSC3 是由 miR-UL112-3p 直接调控的,外源性表达 TUSC3 通过 AKT 信号通路逆转了 miR-UL112-3p 对 GBM 进展的影响。综上所述,这些发现共同表明,miR-UL112-3p 通过直接靶向 GBM 中的 TUSC3 发挥其致癌基因功能,为 GBM 提供了一个潜在的新治疗靶点。