Gao Lei, Wu Jia, Wang Hai, Yang Yongyu, Zheng Zongliao, Ni Bowen, Wang Xiran, Peng Yuping, Li Yaomin
Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Laboratory for Precision Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Front Oncol. 2022 Feb 24;12:770299. doi: 10.3389/fonc.2022.770299. eCollection 2022.
LIM domain only protein1(LMO1), a nuclear transcription coregulator, is implicated in the pathogenesis of T-cell acute lymphoblastic leukemia and neuroblastoma. However, the clinical significance and potential mechanism of LMO1 in human gliomas remain to be determined.
In this study, expression level data and clinical information were obtained three databases. The Cox proportional hazards regression model was used to predict outcomes for glioma patients. and assays were used to explore the function of LMO1 in human glioma. Gene set enrichment analysis (GSEA), RNA-seq and western blot were used to explore the potential molecular mechanisms. A prognostic model was built for predicting the overall survival(OS) of human glioma patients.
High LMO1 expression was associated with a high tumor grade and a poor prognosis in patients. High levels of LMO1 mRNA were correlated with poor prognosis in patients with isocitrate dehydrogenase (IDH)-wild-type (wt) and 1p/19q non-codeletion gliomas. Gene silencing of LMO1 significantly inhibited tumor growth, invasion and migration . In contrast, LMO1 over-expression promoted tumor growth, invasion and migration. Mechanically, LMO1 may positively regulate the level of NGFR mRNA and protein. NGFR mediated the regulation between LMO1 and NF-kB activation. Consistently, the nude mice study further confirmed that knockdown of LMO1 blocked tumor growth NGFR-NF-kB axis. Finally, The nomogram based on the LMO1 signature for overall survival (OS) prediction in human glioma patients exhibited good performance in the individual mortality risk.
This study provides new insights and evidences that high level expression of LMO1 is significantly correlated with progression and prognosis in human gliomas. LMO1 played a critical role in tumorigenesis and progression. The present study first investigated the LMO1-NGFR-NF-kB axis regulate cell growth and invasion in human glioma cells, whereby targeting this pathway may be a therapeutic target for glioma.
仅含LIM结构域蛋白1（LMO1）是一种核转录共调节因子，与T细胞急性淋巴细胞白血病和神经母细胞瘤的发病机制有关。然而，LMO1在人类胶质瘤中的临床意义和潜在机制仍有待确定。
在本研究中，从三个数据库中获取了表达水平数据和临床信息。采用Cox比例风险回归模型预测胶质瘤患者的预后。并通过实验分析来探究LMO1在人类胶质瘤中的功能。利用基因集富集分析（GSEA）、RNA测序和蛋白质免疫印迹法来探究潜在的分子机制。构建了一个预测人类胶质瘤患者总生存期（OS）的预后模型。
LMO1高表达与患者的高肿瘤分级和不良预后相关。LMO1 mRNA高水平与异柠檬酸脱氢酶（IDH）野生型（wt）和1p/√9q非共缺失型胶质瘤患者的不良预后相关。LMO1基因沉默显著抑制肿瘤生长、侵袭和迁移。相反，LMO1过表达促进肿瘤生长、侵袭和迁移。机制上，LMO1可能正向调节神经生长因子受体（NGFR）mRNA和蛋白水平。NGFR介导了LMO1与核因子κB（NF-κB）激活之间的调节作用。同样，裸鼠研究进一步证实，LMO1基因敲低通过NGFR-NF-κB轴阻断肿瘤生长。最后，基于LMO1特征的列线图在预测人类胶质瘤患者总生存期（OS）方面，在个体死亡风险评估中表现良好。
本研究提供了新的见解和证据，表明LMO1的高水平表达与人类胶质瘤的进展和预后显著相关。LMO1在肿瘤发生和进展中起关键作用。本研究首次探究了LMO1-NGFR-NF-κB轴调节人类胶质瘤细胞的生长和侵袭，因此靶向该通路可能成为胶质瘤的治疗靶点。
