MiR-199a-5p targeted regulation of MAGT1 expression in the functional depletion of CD8+T cells in HBV infection.

Abstract

Magnesium transporter 1 (MAGT1) is a key protein that regulates the level of free Mg2+ in cells. Previous studies found that the downregulation of MAGT1 expression in CD8+T cells of HBV patients was correlated with the decrease of intracellular magnesium. However, the expression of MAGT1 mRNA in the CD8+T cells from HBV patients was not significantly altered, indicating that the change in MAGT1 expression was accomplished through posttranscriptional regulation. Through bioinformatics and qRT-PCR detection, miR-199a-5p was found to have a target gene relationship with MAGT1. The expression levels of miR-199a-5p and MAGT1 in HBV infection were evaluated. Lentivirus assays were used to analyze the effects of miR-199a-5p upregulation and downregulation on the MAGT1 expression level and the immune system. Results showed no significant change in the expression of MAGT1 mRNA in HBV-infected cell lines, but the expression of MAGT1 was downregulated. Additionally, the expression level of miR-199a-5p was significantly increased. To this end, we predicted a target relationship between miR-199a-5p and MAGT1 by using TargetScan and verified this relationship through a luciferase activity reporter gene assay. As a result, MAGT1 was found to be the direct target of miR-199a-5p. The targeted inhibition of MAGT1 induced by miR-199a-5p overexpression led to the immune function depletion of CD8+T cells in HBV patients. Downregulating the expression level of miR-199a-5p could effectively improve the functional depletion of CD8+T cells. These findings indicate that miR-199a-5p and MAGT1 could potentially be used as biomarkers for the diagnosis and treatment of chronic HBV infection.