Department of Neurosurgery, China-Japan Union Hospital of Jilin University , Changchun , P.R. China.
Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University , Changchun , P.R. China.
Cell Cycle. 2019 Oct;18(19):2566-2579. doi: 10.1080/15384101.2019.1652046. Epub 2019 Aug 21.
This study is aimed to clarify the potential role of lncRNA LINC00899 in invasion and migration of spinal ependymoma cells through the FoxO pathway via RBL2. Spinal ependymoma related chip data (GSE50161 and GSE66354) was initially downloaded and differentially expressed lncRNAs were screened out. Fifty-eight cases of spinal ependymoma and normal ependymal tissues were collected. The effects of LINC00899 and RBL2 on the spinal ependymoma cell migration and invasion were determined using the third generation spinal ependymoma cells and transfection with LINC00899 vector, siRNA-LINC00899 and siRNA-RBL2. The expression of LINC00899, pathway and cell proliferation- and apoptosis-related factors was determined. Finally, we also detected cell proliferation, migration, invasion, cycle and apoptosis after transfection. Our results showed that LINC00899 was up-regulated in spinal ependymoma and RBL2 was confirmed as a target gene of LINC00899 and found to be involved in regulation of FoxO pathway. LINC00899 expression increased in spinal ependymoma tissues whereas RBL2 expression decreased. Moreover, we found that siRNA-LINC00899 could elevate RBL2, p21, p27 and Bax levels, decrease FoxO, Bcl-2, Vimentin, Annexin levels, reduced cell proliferation, migration and invasion and enhanced apoptosis. Taken together, our study suggests that down-regulated LINC00899 exerts anti-oncogenic effects on spinal ependymoma via RBL2-dependent FoxO, which provides a novel therapeutic target for the treatment of spinal ependymomas.
本研究旨在通过 RBL2 阐明 lncRNA LINC00899 在脊髓室管膜瘤细胞侵袭和迁移中的潜在作用及其对 FoxO 通路的影响。最初下载了与脊髓室管膜瘤相关的芯片数据(GSE50161 和 GSE66354),并筛选出差异表达的 lncRNA。收集了 58 例脊髓室管膜瘤和正常室管膜组织。使用第三代脊髓室管膜瘤细胞和转染 LINC00899 载体、siRNA-LINC00899 和 siRNA-RBL2,确定 LINC00899 和 RBL2 对脊髓室管膜瘤细胞迁移和侵袭的影响。检测 LINC00899、通路和细胞增殖-凋亡相关因子的表达。最后,转染后还检测了细胞增殖、迁移、侵袭、周期和凋亡。结果表明,LINC00899 在脊髓室管膜瘤中呈上调表达,并且 RBL2 被证实为 LINC00899 的靶基因,参与 FoxO 通路的调节。LINC00899 在脊髓室管膜瘤组织中表达增加,而 RBL2 表达降低。此外,我们发现 siRNA-LINC00899 可上调 RBL2、p21、p27 和 Bax 水平,下调 FoxO、Bcl-2、Vimentin、Annexin 水平,降低细胞增殖、迁移和侵袭能力,促进凋亡。综上所述,下调 LINC00899 通过 RBL2 依赖性 FoxO 对脊髓室管膜瘤发挥抑癌作用,为脊髓室管膜瘤的治疗提供了新的治疗靶点。