EIF5A2 specifically regulates the transcription of aging-related genes in human neuroblastoma cells

作者：Yuwei Liu, Li Peng, Jing Chen, Ling Chen, Ying Wu, Mengxin Cheng, Min Chen, Xujun Ye, Yalei Jin · 发表于：BMC Geriatrics · 年份：2023 · DOI：10.1186/s12877-023-03793-6 · 被引用次数：10 · 研究领域：PI3K/AKT/mTOR signaling in cancer、Endoplasmic Reticulum Stress and Disease、Genetics, Aging, and Longevity in Model Organisms

BACKGROUND: Post-transcriptional regulation plays a critical role in controlling biological processes such as aging. Previous studies have shown that eukaryotic initiation factor 5A (EIF5A) might play a crucial role in aging. It is unknown whether EIF5A2, a second isoform of EIF5A, could impact aging through post-transcriptional regulation. METHODS: In the present study, EIF5A2 overexpression (EIF5A2-OE) was induced in SH-SY5Y cells. RNA-seq, bioinformatics analysis and RT-qPCR validation experiments were then performed to explore the molecular mechanism of EIF5A2-mediated transcriptional regulation. Cell viability, proportion of senescent cells and the cell cycle were respectively determined by Cell Counting Kit-8, SA-β‑galactosidase and flow cytometry to evaluate the cell senescence. RESULTS: A total of 190 downregulated and 126 upregulated genes related to EIF5A2-OE were identified. Genes closely related to cellular aging processes such as unfolded protein response (UPR), cell adhesion and calcium signaling pathway were under global transcriptional regulation. Moreover, EIF5A2-OE promoted the viability of SH-SY5Y cells and reduced cell senescence in vitro. Among 30 genes with the most significant expression differences in EIF5A2-OE cells, we identified eight genes, including ASNS, ATF3, ATF4, CEBPB, DDIT3, HERPUD1, HSPA5 and XBP1, enriched in the UPR. Through EIF5A2-tanscription factors (TFs)-targets regulation network in EIF5A2-OE cells, we found three TFs, BHLHE40, RHOXF...