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关键基因与胶质瘤的预后相关,且蜂毒肽可调节胶质瘤U87细胞中这些基因的表达。

Key Genes Are Associated with the Prognosis of Glioma, and Melittin Can Regulate the Expression of These Genes in Glioma U87 Cells.

作者信息

Li Ran, Tao Ting, Ren Qiuyun, Xie Sujun, Gao Xiaofen, Wu Jie, Chen Diling, Xu Changqiong

机构信息

Guangdong Provincial Key Laboratory of Utilization and Conservation of Food and Medicinal Resources in Northern Region, Shaoguan University, 288 Daxue Road, Shaoguan, 512005 Guangdong Province, China.

Medical College of Shaoguan University, 108 XinHua Nan Road, Shaoguan, 512005 Guangdong Province, China.

出版信息

Biomed Res Int. 2022 Dec 31;2022:7033478. doi: 10.1155/2022/7033478. eCollection 2022.

Abstract

Glioma is the most common primary tumor of the central nervous system. Currently, there is no effective treatment for glioma. Melittin (MT) is the main component of bee venom, which was found to have therapeutic effects on a variety of tumors. In this study, we explored the relationship between key genes regulated by MT and the prognosis of glioma. In cultured glioma U87 and U251 cells, MT inhibited cell proliferation and induces cell apoptosis in a time- and concentration-dependent manner. RNA-seq revealed that MT upregulated 11 genes and downregulated 37 genes. These genes are mainly enriched in cell membrane signaling pathways, such as surface membrane, membrane-enclosed organelles, integral component of membrane, PPAR signaling pathway, and voltage-gated potassium channel. PPI network analysis and literature analysis of 48 genes were performed, and 8 key genes were identified, and these key genes were closely associated with clinical prognosis. Overexpression of PCDH18, PPL, DEPP1, VASN, KCNE4, MYBPH, and C5AR2 genes or low expression of MARCH4 gene in glioma patients was associated with poor survival. qPCR confirmed that MT can regulate the expression of these genes in glioma U87 cells. This study indicated that MT significantly inhibited the growth and regulated the expression of PCDH18, C5AR2, VASN, DEPP1, MYBPH, KCNE4, PPL, and MARCH4 genes in glioma U87 cells in vitro. These genes are closely related to the prognosis of patients with glioma and can be used as independent prognostic factors in patients with glioma. MT is a potential drug for the treatment of glioma.

摘要

神经胶质瘤是中枢神经系统最常见的原发性肿瘤。目前,神经胶质瘤尚无有效的治疗方法。蜂毒肽(MT)是蜂毒的主要成分,已发现其对多种肿瘤具有治疗作用。在本研究中,我们探讨了MT调控的关键基因与神经胶质瘤预后之间的关系。在培养的神经胶质瘤U87和U251细胞中,MT以时间和浓度依赖性方式抑制细胞增殖并诱导细胞凋亡。RNA测序显示,MT上调了11个基因,下调了37个基因。这些基因主要富集在细胞膜信号通路中,如表面膜、膜封闭细胞器、膜整合成分、PPAR信号通路和电压门控钾通道。对48个基因进行了蛋白质-蛋白质相互作用(PPI)网络分析和文献分析,确定了8个关键基因,这些关键基因与临床预后密切相关。神经胶质瘤患者中PCDH18、PPL、DEPP1、VASN、KCNE4、MYBPH和C5AR2基因的过表达或MARCH4基因的低表达与较差的生存率相关。定量聚合酶链反应(qPCR)证实,MT可调节神经胶质瘤U87细胞中这些基因的表达。本研究表明,MT在体外显著抑制神经胶质瘤U87细胞的生长,并调节PCDH18、C5AR2、VASN、DEPP1、MYBPH、KCNE4、PPL和MARCH4基因的表达。这些基因与神经胶质瘤患者的预后密切相关,可作为神经胶质瘤患者的独立预后因素。MT是一种治疗神经胶质瘤的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/546f/11401668/c5d673ec901f/BMRI2022-7033478.001.jpg

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