The mechanism of hsa-miR-424-5 combining PD-1 through mTORC signaling pathway to stimulate immune effect and participate in Type 1 diabetes

Abstract

In the present study, hsa-miR-424-5p mimic plasmid and hsa-mir-424-5p inhibitor plasmid were designed and injected into rats respectively, and miRNA control plasmid was also constructed. Models of Type 1 diabetes (T1D) were built. After successful modeling, the expression of hsa-miR-424-5p in lymphocytes was analyzed by RT-PCR. The expression of protein PD-1, T-bet, CXCR3, STING in Th1 lymphocytes and content of IGF-1 in islet tissue were analyzed by flow analysis. The protein levels of SHP2, Rheb, mTORC1, Rictor and Raptor in islet tissue were analyzed by Western blot. The results showed that hsa-miR-424-5p mimic group had the highest expression of hsa-miR-424-5p in lymphocytes. The expression of PD-1 was in hsa-miR-424-5p inhibitor > miRNA control > hsa-miR-424-5p mimic, while the expression of T-bet, CXCR3 and STING was in hsa-miR-424-5p mimic > miRNA control > hsa-miR-424-5p inhibitor. The expression of IGF-1 protein in hsa-miR-424-5p inhibitor group was the highest (32.08%) and hardly expressed in hsa-miR-424-5p mimic group (2.36%). The expression of SHP2, Rheb, mTORC1, Rictor and Raptor of insulin histoproteins were in hsa-miR-424-5p mimic group > miRNA control of > hsa-miR-424-5p inhibitor group, with statistical differences. It indicates that hsa-miR-424-5p binding PD-1 signaling molecules can stimulate the immune effect through the mTORC signaling pathway and participates in the pathogenesis of T1D.

CTRP1 decreases ABCA1 expression and promotes lipid accumulation through the miR‐424‐5p/FoxO1 pathway in THP‐1 macrophage‐derived foam cells

“…Extensive studies have demonstrated that abnormal expression of miRNAs is associated with lipid metabolism disorder and atherosclerosis progression (Aryal et al, 2017; Feinberg & Moore, 2016). Emerging evidence suggests that miR‐424‐5p is involved in metabolic diseases, such as diabetes and obesity (Gasparotto et al, 2019; Wang et al, 2020). Interestingly, miR‐424‐5p is lowly expressed in the peripheral blood isolated from patients and rats with atherosclerosis (Li et al, 2020).…”

“…Emerging evidence suggests that miR-424-5p is involved in metabolic diseases, such as diabetes and obesity (Gasparotto et al, 2019;Wang et al, 2020). Interestingly, miR-424-5p is lowly expressed in the peripheral blood isolated from patients and rats with atherosclerosis (Li et al, 2020).…”

Interplay Between Non-Coding RNAs and Programmed Cell Death Proteins

“…hsa-miR-424-5p has been found to bind with PD-1 stimulating immune responses through the mTORC signal transduction, thus participating in the pathoetiology of type I diabetes ( 34 ). Similarly, up-regulation of miR-28 by targeting PD-1 and regulating cytokine secretion could modulate exhaustive differentiation of T cells ( 35 ).…”

microRNAs involved in T‐cell development, selection, activation, and hemostasis

“…The miRNAs have an essential role in the regulation of PD‐1 expression (Figure 3d). The evaluation of miRNAs in lymphocyte‐derived from the diabetic mice model indicated that the elevated level of miR‐424‐5p has a negative correlation with the pathogenesis of type 1 diabetes by downregulating of PD‐1 (G. Wang, Yan, Zheng, & Zhang, 2020). Furthermore, miRNAs are involved in the suppression of cancer progression by decreasing the PD‐1 levels.…”