Department of Neurosurgery, Gaozhou People's Hospital, Gaozhou, 525200, Guangdong, China.
Department of Gastroenterology, Gaozhou People's Hospital, Gaozhou, 525200, Guangdong, China.
Cell Death Dis. 2021 Jan 22;12(1):115. doi: 10.1038/s41419-020-03163-9.
Glioblastoma multiforme (GBM) brings serious physical and psychological pain to GBM patients, whose survival rate remains not optimistic. Long noncoding RNAs (lncRNAs) have been reported to participate in the progression of many cancers, including GBM. However, the mechanism and function of long intergenic non-protein coding RNA 1152 (LINC01152) in GBM are still unclear. In our study, we aimed to explore the function and mechanism of LINC01152 in GBM. Then qRT-PCR analysis was implemented to search the expression of RNAs in GBM tissues and cells. Functional assays such as EdU assay, colony formation assay, TUNEL assay and flow cytometry analysis were conducted to estimate GBM cell proliferation and apoptosis. RNA pull down assay, luciferase reporter assay, RIP and ChIP assays were implemented to search the binding between molecules. As a result, we discovered that LINC01152 was upregulated in GBM tissues and cells. LINC01152 and mastermind like transcriptional coactivator 2 (MAML2) could both play the oncogenic part in GBM. Moreover, LINC01152 positively regulated MAML2 in GBM by sponging miR-466 and recruiting SRSF1. In turn, RBPJ/MAML2 transcription complex was found to activate the transcription of LINC01152 in GBM cells. In conclusion, LINC01152 could upregulate the expression of MAML2 to promote tumorigenesis in GBM via Notch signaling pathway.
多形性胶质母细胞瘤（GBM）给 GBM 患者带来了严重的身体和心理痛苦，其生存率仍然不容乐观。长链非编码 RNA（lncRNA）已被报道参与许多癌症的进展，包括 GBM。然而，长基因间非蛋白编码 RNA 1152（LINC01152）在 GBM 中的作用和机制仍不清楚。在我们的研究中，我们旨在探讨 LINC01152 在 GBM 中的功能和机制。然后，通过 qRT-PCR 分析搜索 GBM 组织和细胞中 RNA 的表达。通过 EdU 测定、集落形成测定、TUNEL 测定和流式细胞术分析等功能测定来评估 GBM 细胞的增殖和凋亡。通过 RNA 下拉测定、荧光素酶报告测定、RIP 和 ChIP 测定来搜索分子之间的结合。结果发现，LINC01152 在 GBM 组织和细胞中上调。LINC01152 和主脑样转录共激活因子 2（MAML2）均可在 GBM 中发挥致癌作用。此外，LINC01152 通过海绵 miR-466 和募集 SRSF1 正向调节 GBM 中的 MAML2。反过来，RBPJ/MAML2 转录复合物被发现激活 GBM 细胞中 LINC01152 的转录。总之，LINC01152 可通过 Notch 信号通路上调 MAML2 的表达，促进 GBM 肿瘤发生。
