Qingdao University, Qingdao, Shandong, 266003, China; Department of Neurosurgery, Weifang People's Hospital, Weifang, Shandong, 261041, China.
Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, China.
Biomed Pharmacother. 2018 Sep;105:677-682. doi: 10.1016/j.biopha.2018.06.005. Epub 2018 Jun 12.
Emerging evidence reveal that long noncoding RNAs (lncRNAs) participates in the epigenetic regulation of pathophysiological process. However, the deepgoing role of lncRNAs on meningioma is still unclear. In present study, we investigate the roles of lncRNA LINC00460 in meningeoma tissue and uncover its molecular mechanism. Results revealed that LINC00460 expression level was significantly up-regulated in meningeoma tissues and malignant meningeoma cell lines (IOMM-Lee, CH157-MN). Mechanically, loss-of-function assays showed that LINC00460 knockdown significantly suppressed the proliferation ability, increased the apoptosis and decreased the proteins (MMP-2, MMP-9, ZEB1) expression. Bioinformatics tools predicted that miR-539 both targeted with the 3'-UTR of LINC00460 and MMP-9 mRNA, which was confirmed by luciferase reporter assay and western blot analysis. In summary, our study reveals that LINC00460 promotes MMP-9 expression through targeting miR-539, acting as an oncogenic RNA in the meningeoma malignancy and accelerating the proliferation and metastasis of meningeoma.
新出现的证据表明，长非编码 RNA（lncRNA）参与了病理生理过程的表观遗传调控。然而，lncRNA 对脑膜瘤的深入作用尚不清楚。在本研究中，我们研究了 lncRNA LINC00460 在脑膜瘤组织中的作用，并揭示了其分子机制。结果显示，LINC00460 在脑膜瘤组织和恶性脑膜瘤细胞系（IOMM-Lee、CH157-MN）中的表达水平显著上调。功能丧失实验表明，LINC00460 敲低显著抑制了增殖能力，增加了细胞凋亡，并降低了蛋白质（MMP-2、MMP-9、ZEB1）的表达。生物信息学工具预测 miR-539 与 LINC00460 的 3'-UTR 和 MMP-9 mRNA 均靶向结合，这通过荧光素酶报告基因检测和 Western blot 分析得到了证实。总之，我们的研究表明，LINC00460 通过靶向 miR-539 促进 MMP-9 表达，作为脑膜瘤恶性肿瘤中的致癌 RNA，加速脑膜瘤的增殖和转移。
