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Abstract：
BACKGROUND: 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.
CONCLUSIONS: Altogether, these findings demonstrate that HEC1 may be a potential prognostic marker and an immunotherapeutic target in glioma.
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.
CONCLUSIONS: Altogether, these findings demonstrate that HEC1 may be a potential prognostic marker and an immunotherapeutic target in glioma.
摘要：
背景：胶质瘤是原发性脑肿瘤的最常见和致死形式。胶质瘤发生发展的分子机制尚不清楚,呈现常规放疗的治疗效果，化疗,手术切除不足。在这项研究中,我们试图探索HEC1(在癌症1中高表达)在神经胶质瘤中的功能;神经胶质瘤中NDC80复合物的一个成分在动粒的调节中至关重要.
方法：使用BulkRNA和scRNA-seq分析来推断HEC1功能，体外实验验证了其功能。
结果：在神经胶质瘤中观察到HEC1过度表达，表明预后不良和恶性临床特征，这在人类神经胶质瘤组织中得到证实。高HEC1表达与更活跃的细胞周期相关，DNA相关活动,和免疫抑制肿瘤微环境的形成，包括与免疫细胞的相互作用，并与浸润的免疫细胞和免疫检查点的表达增强密切相关。体外实验和RNA-seq进一步证实了HEC1在促进细胞增殖中的作用,以及神经胶质瘤中DNA复制和修复通路的表达。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。
结论：总而言之，这些发现表明HEC1可能是神经胶质瘤的潜在预后标志物和免疫治疗靶点.
方法：使用BulkRNA和scRNA-seq分析来推断HEC1功能，体外实验验证了其功能。
结果：在神经胶质瘤中观察到HEC1过度表达，表明预后不良和恶性临床特征，这在人类神经胶质瘤组织中得到证实。高HEC1表达与更活跃的细胞周期相关，DNA相关活动,和免疫抑制肿瘤微环境的形成，包括与免疫细胞的相互作用，并与浸润的免疫细胞和免疫检查点的表达增强密切相关。体外实验和RNA-seq进一步证实了HEC1在促进细胞增殖中的作用,以及神经胶质瘤中DNA复制和修复通路的表达。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。
结论：总而言之，这些发现表明HEC1可能是神经胶质瘤的潜在预后标志物和免疫治疗靶点.
