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

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.