Exploring the Potential Mechanism of Apoptosis Induced by MFSD8 in Endothelial Cells: an RNA Sequencing and Bioinformatics Analysis

IF 1.5 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Biology Pub Date : 2024-05-02 DOI:10.1134/s0026893324700225

Q. Xiang, Y. Liu, S. S. Jiang, Y. F. Chen, Y. X. Liu, D. W. Yang, L. Tang, J. M. Li

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Abstract

Neuronal ceroid lipofuscinoses (NCLs) belong to a group of inherited neurodegenerative disorders without effective treatments. Though loss-of-function in the MFSD8 gene resulting in a variant late-infantile subtype of NCLs is well documented, its roles remain poorly explored and understood. The results showed an increased cell apoptosis rate after the MFSD8 gene low expression in HUVECs by Flow cytometric analysis. RNA sequencing revealed 367 differentially expressed genes upon the MFSD8 gene overexpression in HUVECs. Bioinformatics analyses revealed that the MFSD8 gene overexpression might be involved in the PI3K/Akt signaling pathway, and interleukin-6 (IL-6), interleukin-1 beta (IL-1B), fibronectin 1 (FN1), fibroblast growth factor 2 (FGF2), toll-like receptor 4 (TLR4), tumor necrosis factor (TNF), and prostaglandin G/H synthase 2 (PTGS2) were the potential hub genes affected by the MFSD8 gene. Gene set enrichment analysis and qRT-PCR assay validation also disclosed that the “Hallmark_Apoptosis” pathway was dramatically enriched in differentially expressed genes. The results revealed that the loss of functional MFSD8 protein indirectly or directly increased the apoptosis of HUVECs, indicating that the expression of the MFSD8 gene was essential for cell survival. The hub genes, including IL-6, IL-1B, FN1, FGF2, TLR4, TNF, and PTGS2, might provide insight into the apoptosis induced by the MFSD8 gene in NCLs. Although many experiments are required to validate these predictions, the results may help investigate the roles of the MFSD8 gene on apoptosis and the corresponding mechanism.

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探索MFSD8诱导内皮细胞凋亡的潜在机制：RNA测序和生物信息学分析

摘要神经元类色素沉着症（NCLs）是一类遗传性神经退行性疾病，目前尚无有效的治疗方法。尽管MFSD8基因的功能缺失导致了一种变异的晚发型NCLs亚型，但对其作用的探索和了解仍然很少。结果显示，通过流式细胞分析，MFSD8 基因在 HUVECs 中低表达后，细胞凋亡率增加。RNA 测序显示，MFSD8 基因在 HUVECs 中过表达后，367 个基因有不同表达。生物信息学分析表明，MFSD8基因过表达可能参与了PI3K/Akt信号通路，白细胞介素-6（IL-6）、白细胞介素-1 beta（IL-1B）、纤连蛋白1（FN1）、成纤维细胞生长因子2（FGF2）、类收费受体4（TLR4）、肿瘤坏死因子（TNF）和前列腺素G/H合成酶2（PTGS2）是受MFSD8基因影响的潜在枢纽基因。基因集富集分析和qRT-PCR检测验证也显示，"Hallmark_Apoptosis "通路在差异表达基因中显著富集。结果显示，功能性 MFSD8 蛋白的缺失间接或直接增加了 HUVECs 的凋亡，表明 MFSD8 基因的表达对细胞存活至关重要。包括IL-6、IL-1B、FN1、FGF2、TLR4、TNF和PTGS2在内的枢纽基因可能有助于了解MFSD8基因在NCL中诱导细胞凋亡的情况。尽管还需要许多实验来验证这些预测，但这些结果可能有助于研究 MFSD8 基因对细胞凋亡的作用及其相应的机制。

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来源期刊

Molecular Biology 生物-生化与分子生物学

CiteScore

1.30

自引率

8.30%

发文量

审稿时长

3 months

期刊介绍： Molecular Biology is an international peer reviewed journal that covers a wide scope of problems in molecular, cell and computational biology including genomics, proteomics, bioinformatics, molecular virology and immunology, molecular development biology, molecular evolution and related areals. Molecular Biology publishes reviews, experimental and theoretical works. Every year, the journal publishes special issues devoted to most rapidly developing branches of physical-chemical biology and to the most outstanding scientists.