Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, PR China.
Oncol Rep. 2013 Aug;30(2):870-6. doi: 10.3892/or.2013.2526. Epub 2013 Jun 7.
Glioblastoma (GBM) is one of the most lethal forms of human cancer, and new clinical biomarkers and therapeutic targets are urgently required. microRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional and/or translational level by binding the 3' untranslated regions (3' UTRs) of target mRNAs. The dysregulated expression of several miRNAs has been reported to modulate glioma progression. In the present study, we defined the expression and function of miR-708, which, based on real-time PCR analysis, were downregulated in GBM cells. The overexpression of miR-708 inhibited cell proliferation and invasion and induced apoptosis in the human GBM cell lines A172 and T98G. Furthermore, the overexpression of miR-708 reduced the expression of Akt1, CCND1, MMP2, EZH2, Parp-1 and Bcl2 in A172 and T98G cells. Taken together, our study suggests that miR-708 affects GBM cell proliferation and invasion, and induces apoptosis. It is suggested that miR-708 may play an important role as a tumor suppressor in GBM and it may be an attractive target for therapeutic intervention in GBM.
胶质母细胞瘤(GBM)是人类癌症中最致命的形式之一,迫切需要新的临床生物标志物和治疗靶点。microRNAs(miRNAs)是小的非编码 RNA,通过与靶 mRNA 的 3'非翻译区(3'UTR)结合,在转录后和/或翻译水平上负调控基因表达。据报道,几种 miRNAs 的表达失调可调节神经胶质瘤的进展。在本研究中,我们定义了 miR-708 的表达和功能,基于实时 PCR 分析,miR-708 在 GBM 细胞中表达下调。miR-708 的过表达抑制了人 GBM 细胞系 A172 和 T98G 的增殖和侵袭,并诱导了细胞凋亡。此外,miR-708 的过表达降低了 A172 和 T98G 细胞中 Akt1、CCND1、MMP2、EZH2、Parp-1 和 Bcl2 的表达。综上所述,我们的研究表明 miR-708 影响 GBM 细胞的增殖和侵袭,并诱导细胞凋亡。提示 miR-708 可能作为 GBM 的肿瘤抑制因子发挥重要作用,可能成为 GBM 治疗干预的有吸引力的靶点。