HIV-1 Tat and cocaine impact astrocytic energy reservoir influence on miRNA epigenetic regulation

Astrocytes are the primary regulator of energy metabolism in the central nervous system (CNS), and impairment of astrocyte's energy resource may trigger neurodegeneration. HIV infections and cocaine use are known to alter epigenetic modification, including miRNAs, which can target gene expression post-transcriptionally. However, miRNA-mediated astrocyte energy metabolism has not been delineated in HIV infection and cocaine abuse. Using next-generation sequencing (NGS), we identified a total of 1900 miRNAs, 64 were upregulated and 68 miRNAs were downregulated in the astrocytes by HIV-1 Tat with cocaine exposure. Moreover, miR-4727-3p, miR-5189-5p, miR-5090, and miR-6810-5p expressions were significantly impacted, and their gene targets were identified as VAMP2, NFIB, PPM1H, MEIS1, and PSD93 through the bioinformatic approach. In addition, the astrocytes treated with the nootropic drug piracetam protects these miRNAs. These findings provide evidence that the miRNAs in the astrocytes may be a potential biomarker and therapeutic target for HIV and cocaine abuse-induced neurodegeneration. •HIV-1 Tat with cocaine exposure to astrocytes downregulated 68 and upregulated 64 miRNAs out of 1900 miRNAs•miR-4727-3p, miR-5189-5p, miR-5090, and miR-6810-5p were significantly impacted due to exposure of HIV-1 Tat with cocaine.•VAMP2, NFIB, PPM1H, MEIS1, and PSD93, which are significant gene targets of these miRNAs.•Differentially expressed miRNAs regulate astrocyte energy metabolism.