NDC80/HEC1 通过单细胞 RNA-seq 和体外实验促进巨噬细胞极化并预测胶质瘤预后。

NDC80/HEC1 promotes macrophage polarization and predicts glioma prognosis via single-cell RNA-seq and in vitro experiment.

机构信息

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.

Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China.

出版信息

CNS Neurosci Ther. 2024 Jul;30(7):e14850. doi: 10.1111/cns.14850.

DOI:10.1111/cns.14850

PMID:39021287

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11255415/

Abstract

INTRODUCTION

Glioma is the most frequent and lethal form of primary brain tumor. The molecular mechanism of oncogenesis and progression of glioma still remains unclear, rendering the therapeutic effect of conventional radiotherapy, chemotherapy, and surgical resection insufficient. In this study, we sought to explore the function of HEC1 (highly expressed in cancer 1) in glioma; a component of the NDC80 complex in glioma is crucial in the regulation of kinetochore.

METHODS

Bulk RNA and scRNA-seq analyses were used to infer HEC1 function, and in vitro experiments validated its function.

RESULTS

HEC1 overexpression was observed in glioma and was indicative of poor prognosis and malignant clinical features, which was confirmed in human glioma tissues. High HEC1 expression was correlated with more active cell cycle, DNA-associated activities, and the formation of immunosuppressive tumor microenvironment, including interaction with immune cells, and correlated strongly with infiltrating immune cells and enhanced expression of immune checkpoints. In vitro experiments and RNA-seq further confirmed the role of HEC1 in promoting cell proliferation, and the expression of DNA replication and repair pathways in glioma. Coculture assay confirmed that HEC1 promotes microglial migration and the transformation of M1 phenotype macrophage to M2 phenotype.

CONCLUSION

Altogether, these findings demonstrate that HEC1 may be a potential prognostic marker and an immunotherapeutic target in glioma.

摘要

简介

神经胶质瘤是最常见和最致命的原发性脑肿瘤。神经胶质瘤发生和进展的分子机制仍不清楚，这使得传统放疗、化疗和手术切除的治疗效果不足。在这项研究中，我们试图探讨 HEC1（癌症高表达 1）在神经胶质瘤中的功能；神经胶质瘤中的 NDC80 复合物的一个组成部分在调节着丝粒方面起着关键作用。

方法

使用 bulk RNA 和 scRNA-seq 分析来推断 HEC1 的功能，并通过体外实验验证其功能。

结果

在神经胶质瘤中观察到 HEC1 的过表达，并且与不良预后和恶性临床特征相关，这在人类神经胶质瘤组织中得到了证实。高 HEC1 表达与更活跃的细胞周期、与 DNA 相关的活性以及免疫抑制性肿瘤微环境的形成相关，包括与免疫细胞的相互作用，并且与浸润性免疫细胞和免疫检查点的增强表达密切相关。体外实验和 RNA-seq 进一步证实了 HEC1 在促进神经胶质瘤细胞增殖以及 DNA 复制和修复途径表达中的作用。共培养实验证实 HEC1 促进小胶质细胞迁移和 M1 表型巨噬细胞向 M2 表型的转化。