解析胶质母细胞瘤中YY1/lncRNA BLACAT1/miR-605-3p轴：对治疗的意义

Deciphering the YY1/ lncRNA BLACAT1/miR-605-3p axis in glioblastoma: implications for therapy.

作者信息

Han Liang, Wang Han, Xie Hong, Yu Xiuming, Zhou Haixia, Guo Zhigang

机构信息

Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, China.

Department of Clinical Laboratory, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, 130021, China.

出版信息

NPJ Precis Oncol. 2025 Jul 1;9(1):213. doi: 10.1038/s41698-025-01001-9.

DOI:10.1038/s41698-025-01001-9

PMID:40595024

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12215738/

Abstract

Glioblastoma multiforme (GBM), an aggressive brain cancer, requires novel therapeutic targets. This study investigates the YY1/lncRNA BLACAT1/miR-605-3p regulatory network in GBM pathogenesis. Using bioinformatics tools and TCGA-GBM datasets, we identified six miR-605-3p target genes (ARPC1B, FOSL1, H6PD, ITGA3, LMAN1, and PXN) strongly correlated with YY1 (p < 0.01). In GBM cells, YY1 mRNA increased ~3.8-fold (p < 0.01), BLACAT1 ~ 2.4-2.7-fold (p < 0.01), and target genes ~1.8-2.5-fold (p < 0.05), while miR-605-3p decreased to ~0.3-fold (p < 0.01). YY1 knockout reduced BLACAT1 to 0.33 (p < 0.001), reversed by miR-605-3p inhibition. YY1 knockout inhibited migration (53-75%, p < 0.001), invasion (53-62%, p < 0.001), colony formation (43-53%, p < 0.001), and angiogenesis (p < 0.01). In U251 xenograft models, YY1 knockout reduced tumor volume from 2036 to 260 mm³ (p < 0.0001), partially restored to 1558 mm³ (p < 0.0001) by miR-605-3p antagomir, while agomir reduced it to 721 mm³ (p < 0.01). YY1 promoted angiogenesis, oxidative stress, inflammation, and fibrosis (p < 0.05), countered by miR-605-3p (p < 0.05). Validations included RT-qPCR, ChIP-qPCR, immunofluorescence, dual-luciferase assays, and immunohistochemistry. The YY1/BLACAT1/miR-605-3p axis drives GBM progression, offering therapeutic potential.

摘要

多形性胶质母细胞瘤（GBM）是一种侵袭性脑癌，需要新的治疗靶点。本研究调查了YY1/lncRNA BLACAT1/miR-605-3p调控网络在GBM发病机制中的作用。利用生物信息学工具和TCGA-GBM数据集，我们鉴定出六个与YY1高度相关的miR-605-3p靶基因（ARPC1B、FOSL1、H6PD、ITGA3、LMAN1和PXN）（p < 0.01）。在GBM细胞中，YY1 mRNA增加约3.8倍（p < 0.01），BLACAT1增加约2.4 - 2.7倍（p < 0.01），靶基因增加约1.8 - 2.5倍（p < 0.05），而miR-605-3p降至约0.3倍（p < 0.01）。YY1基因敲除使BLACAT1降至0.33（p < 0.001），miR-605-3p抑制可使其逆转。YY1基因敲除抑制迁移（53 - 75%，p < 0.001）、侵袭（53 - 62%，p < 0.001）、集落形成（43 - 53%，p < 0.001）和血管生成（p < 0.01）。在U251异种移植模型中，YY1基因敲除使肿瘤体积从2036降至260 mm³（p < 0.0001），miR-605-3p拮抗剂可使其部分恢复至1558 mm³（p < 0.0001），而激动剂可使其降至721 mm³（p < 0.01）。YY1促进血管生成、氧化应激、炎症和纤维化（p < 0.05），miR-605-3p可对抗这些作用（p < 0.05）。验证方法包括RT-qPCR、ChIP-qPCR、免疫荧光、双荧光素酶测定和免疫组织化学。YY1/BLACAT1/miR-605-3p轴驱动GBM进展，具有治疗潜力。