Department of Neurosurgery, Ganzhou People's Hospital, Ganzhou, 341000, China; Department of Central Laboraotory, Fuling Central Hospital of Chongqing City, Chongqing, 408099, China; Second Clinical College, Chongqing Medical University, Chongqing, 400010, China.
Department of Radiology, Fuling Central Hospital of Chongqing City, Chongqing, 408099, China.
Pathol Res Pract. 2019 Oct;215(10):152558. doi: 10.1016/j.prp.2019.152558. Epub 2019 Jul 23.
Glioma is a common and fatal intracranial tumor. Both miR-377 and lncRNA MEG3 are tumor suppressors. This study was performed to investigate the association between miR-377 and lncRNA MEG3 in glioma cells.
U118 and U251 cell lines were incubated in Dulbecco's modified Eagle's medium supplemented with miR-377 mimics, MEG3 siRNA (si-MEG3) and/or MEG3 overexpression plasmids (pc-MEG3) for 48 h. Cell migration, invasion, apoptosis, cell cycle distribution and the expression of E26 tansformation-specific-1 (ETS-1), phosphatase and tensin homologue (PTEN), E-cadherin, N-cadherin and β-catenin were detected.
MiR-377 mimics increased MEG3 expression and decreased the number of migrated and invaded U118 and U251 cells, without influence on apoptosis in both cell lines. Si-MEG3 transfection increased U118 cell migration and invasion and rescued miR-377 mimics-induced inhibitory in cell migration and invasion. Si-MEG3 decreased U118 cell apoptosis and induced G0/G1 cell cycle arrest, and pc-MEG3 increased U251 cell apoptosis via arresting cell cycle at G2/M phage. MiR-377 mimics and si-MEG3 increased the relative expression level of N-cadherin mRNA, and both si-MEG3 and pc-MEG3 increased E-cadherin in glioma cells. MiR-377 mimics increased ETS-1 mRNA in U118 cells, but decreased it in U251 cells. PTEN was increased by miR-377 mimics and si-MEG3 and decreased by pc-MEG3 in glioma cells.
These results suggested the link interaction of MEG3 with miR-377 and PTEN, but not functioning as the competing endogenous RNA. MiR-377 mimics and MEG3 were tumor suppressors in glioma cells through regulating PTEN expression.
神经胶质瘤是一种常见且致命的颅内肿瘤。miR-377 和 lncRNA MEG3 均为肿瘤抑制因子。本研究旨在探讨 miR-377 与神经胶质瘤细胞中的 lncRNA MEG3 之间的关系。
将 U118 和 U251 细胞系在补充有 miR-377 模拟物、MEG3 siRNA（si-MEG3）和/或 MEG3 过表达质粒（pc-MEG3）的 Dulbecco 改良 Eagle 培养基中孵育 48 小时。检测细胞迁移、侵袭、凋亡、细胞周期分布以及 E26 转化特异性-1（ETS-1）、磷酸酶和张力蛋白同源物（PTEN）、E-钙黏蛋白、N-钙黏蛋白和 β-连环蛋白的表达。
miR-377 模拟物增加了 MEG3 的表达，减少了 U118 和 U251 细胞的迁移和侵袭数量，但对两种细胞系的凋亡均无影响。si-MEG3 转染增加了 U118 细胞的迁移和侵袭，并挽救了 miR-377 模拟物诱导的迁移和侵袭抑制。si-MEG3 降低了 U118 细胞的凋亡并诱导 G0/G1 细胞周期停滞，而 pc-MEG3 通过将 U251 细胞周期阻滞在 G2/M 期增加了细胞凋亡。miR-377 模拟物和 si-MEG3 增加了 N-钙黏蛋白 mRNA 的相对表达水平，si-MEG3 和 pc-MEG3 均增加了神经胶质瘤细胞中的 E-钙黏蛋白。miR-377 模拟物增加了 U118 细胞中 ETS-1 mRNA 的表达，但降低了 U251 细胞中的表达。miR-377 模拟物和 si-MEG3 增加了神经胶质瘤细胞中的 PTEN，而 pc-MEG3 则降低了其表达。
这些结果表明 MEG3 与 miR-377 和 PTEN 之间存在相互作用关系，但不作为竞争性内源 RNA 发挥作用。miR-377 模拟物和 MEG3 通过调节 PTEN 表达在神经胶质瘤细胞中起肿瘤抑制作用。
