Li Peng, Yang Yang, Luan Chunpeng, Wang Wenbin, Jiang Yuan, Zhao Zhenhao, Wang Bo, Zhao Yuting, Bai Yunlong, Liu Man, Zhao Zhongfang, Zhang Lei, Qian Yuyang, Shi Jiandang
College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China.
Department of Maxillofacial and Otorhinolaryngological Oncology, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin, Tianjin, China.
Oncogenesis. 2025 Apr 7;14(1):8. doi: 10.1038/s41389-025-00551-8.
Glioblastoma (GBM) is one of the most malignant primary brain tumors, and factors governing its progression are not fully characterized. Recent research suggests that the long non-coding RNA (lncRNA) HOTAIR and super-enhancers (SEs) contribute significantly to GBM progression. Here, we performed TCGA data analysis revealing that high HOTAIR expression in GBM is associated with poor prognosis. Conversely, HOTAIR knock-down (KD) decreased proliferation, colony formation, and invasion of GBM cells. Furthermore, RNA-seq analysis identified DEGs in GBM cells related to cell growth and adhesion. Using an integrated approach, we also identify MEST as a HOTAIR-associated SE target gene. Intriguingly, MEST suppression in GBM cells phenocopied HOTAIR KD, as evidenced by reduced cell proliferation and invasion, whereas MEST overexpression counteracted effects of HOTAIR depletion. Moreover, 3 C technique-based PCR confirmed reduced interaction between HOTAIR-associated SEs and target genes after HOTAIR KD. This study reveals a novel regulatory mechanism governing GBM, offering promising directions for clinical interventions.
胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤之一，其进展相关因素尚未完全明确。近期研究表明，长链非编码RNA（lncRNA）HOTAIR和超级增强子（SEs）在GBM进展中起重要作用。在此，我们通过对癌症基因组图谱（TCGA）数据分析发现，GBM中HOTAIR高表达与预后不良相关。相反，HOTAIR基因敲低（KD）可降低GBM细胞的增殖、集落形成和侵袭能力。此外，RNA测序分析确定了GBM细胞中与细胞生长和黏附相关的差异表达基因（DEGs）。通过综合分析，我们还确定了MEST是一个与HOTAIR相关的SE靶基因。有趣的是，GBM细胞中MEST的抑制表现与HOTAIR KD相似，表现为细胞增殖和侵袭能力降低，而MEST过表达则可抵消HOTAIR缺失的影响。此外，基于3C技术的PCR证实HOTAIR KD后，HOTAIR相关SE与靶基因之间的相互作用减少。本研究揭示了一种新的GBM调控机制，为临床干预提供了有前景的方向。
