EIF4A3-induced hsa_circ_0127071 promotes human glomerular mesangial cells senescence via JAK2/STAT5 signaling pathway

Increasing evidence has revealed a close relationship between circular RNAs (circRNAs) and the regulatory process of cell aging. Exploring the role and mechanism of circRNAs in cellular senescence may help to identify new anti-aging therapeutic targets. In the present study, we investigated the role and regulatory mechanism of hsa_circ_012707 in renal aging.High-throughput sequencing was performed to detect the differential expression of circRNAs in kidney tissues of the old and young groups. qRT-PCR confirmed that the expression of hsa_circ_0127071 in kidney tissue of the old group was significantly higher than that of the young group. SA-β-Gal, Masson Assay is used to evaluate the role of hsa_circ_0127071 in the aging process of kidney tissue.Using RIP, RNA pull down, and WB to study the interaction between hsa_circ_0127071 and aging related pathway proteins.In this study, we found that the expression of hsa_circ_0127071 in kidney tissue of the old group was significantly higher than that of the young group. The activity of JAK2/STAT5 signaling pathway was decreased after silencing EIF4A3, which could delay the aging process. On the basis of silencing EIF4A3 expression, the JAK2/STAT5 signaling pathway was activated by EPO processing, and the senescence of HGMCs increased. After treatment with LOS, the activity of JAK2/STAT5 pathway was decreased and the aging process of HGMCs was delayed. Our findings showed that hsa_circ_0127071 promoted renal aging, and confirmed the regulatory role of EIF4A3/hsa_circ_0127071/JAK2/STAT5 in the regulation of renal aging, providing a new therapeutic target for drug design and early diagnosis. In conclusion, this study intends to use human kidney tissues and human mesangial cells for validation experiments through transcriptional gene assay, KEGG pathway and other prediction, aiming to explore that EIF4A3-induced hsa_circ_0127071 promotes human glomerular mesangial cells senescence via JAK2/STAT5 signaling pathway. in order to provide a new therapeutic target for the prevention and treatment of renal aging.