LMO1 Plays an Oncogenic Role in Human Glioma Associated With NF-kB Pathway

作者：Lei Gao, Jia Qian Wu, Hai Wang, Yong‐Yu Yang, Zongliao Zheng, Bowen Ni, Xiran Wang, Yu-Ping Peng, Yaomin Li · 发表于：Frontiers in Oncology · 年份：2022 · DOI：10.3389/fonc.2022.770299 · 被引用次数：7 · 研究领域：Protein Degradation and Inhibitors、Cancer Mechanisms and Therapy、Nuclear Receptors and Signaling

Background 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. Methods In this study, expression level data and clinical information were obtained via three databases. The Cox proportional hazards regression model was used to predict outcomes for glioma patients. In vitro and in vivo 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. Results 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 vitro . 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 via NGFR-NF-kB axis. Finally, The nomogra...