Hong Li, Ya-Wei Liu, Hai Wang, Qiang Zhou, Jun-Jie Li, Huang Annie, Song-Tao Qi, Yun-Tao Lu
Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Nanfang Neurology Research Institution, Nanfang Hospital, Guangzhou, China.
J Neurooncol. 2016 May;128(1):35-45. doi: 10.1007/s11060-016-2095-z. Epub 2016 Mar 12.
Glioblastoma (GBM) is among the most aggressive primary brain tumors, with a median survival rate of 12-15 months. MicroRNAs have been implicated in GBM development as oncogenes or tumor suppressors. In this study, we demonstrated that miR-519a expression was frequently downregulated in GBM specimens and cell lines, and that low-levels miR-519a expression significantly correlated with poor outcomes associated with GBM. Analysis of The Cancer Genome Atlas also demonstrated that low miR-519a expression can predict poor clinical outcomes in classical and proneural GBM subtypes. Functionally, re-expression of miR-519a effectively reduced GBM cell proliferation, migration, and invasion. Mechanistically, we confirmed that the signal transducer and activator of transcription 3 (STAT3) 3'-UTR was a putative target of miR-519a, and that re-expression of STAT3 abrogated miR-519a function in GBM cells. Furthermore, we found that STAT3 expression negatively correlated with that of miR-519a in human GBM tissues. These results elucidated the prognostic value and tumor-suppressor role of miR-519a in GBM and further suggested it as a potential therapeutic target for GBM treatment.
胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤之一，中位生存期为12 - 15个月。微小RNA已被认为在GBM的发生发展中作为癌基因或肿瘤抑制因子发挥作用。在本研究中，我们证明miR - 519a在GBM标本和细胞系中表达常常下调，并且低水平的miR - 519a表达与GBM相关的不良预后显著相关。对癌症基因组图谱的分析也表明，低miR - 519a表达可预测经典型和神经干细胞型GBM亚型的不良临床结局。在功能上，miR - 519a的重新表达有效降低了GBM细胞的增殖、迁移和侵袭。机制上，我们证实信号转导和转录激活因子3（STAT3）的3'-UTR是miR - 519a的一个假定靶点，并且STAT3的重新表达消除了miR - 519a在GBM细胞中的功能。此外，我们发现STAT3在人类GBM组织中的表达与miR - 519a呈负相关。这些结果阐明了miR - 519a在GBM中的预后价值和肿瘤抑制作用，并进一步表明它是GBM治疗的潜在治疗靶点。
