HIV-1 Tat and cocaine impact astrocytic energy reservoir influence on miRNA epigenetic regulation.
HIV-1 Tat and cocaine impact astrocytic energy reservoir influence on miRNA epigenetic regulation.
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DOI：
10.1016/j.ygeno.2021.08.013
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发表时间：
2021-11
期刊：
影响因子：
4.4
通讯作者：
Samikkannu T
中科院分区：
文献类型：
--
作者：
Doke M;Kashanchi F;Khan MA;Samikkannu T
星形胶质细胞是中枢神经系统（CNS）能量代谢的主要调节者，星形胶质细胞的能量来源受损可能会引发神经退行性变。众所周知，HIV 感染和可卡因使用会改变表观遗传修饰，包括可以靶向转录后基因表达的 miRNA。然而，miRNA 介导的星形胶质细胞能量代谢在 HIV 感染和可卡因滥用中尚未得到证实。使用下一代测序 (NGS)，我们在星形胶质细胞中总共鉴定了 1900 个 miRNA，其中 64 个 miRNA 上调，68 个 miRNA 在接触可卡因的 HIV-1 Tat 中下调。此外，miR-4727-3p、miR-5189-5p、miR-5090和miR-6810-5p的表达受到显着影响，通过生物信息学方法将其靶基因确定为VAMP2、NFIB、PPM1H、MEIS1和PSD93。此外，用促智药物吡拉西坦处理的星形胶质细胞可以保护这些 miRNA。这些发现提供的证据表明，星形胶质细胞中的 miRNA 可能是 HIV 和可卡因滥用引起的神经变性的潜在生物标志物和治疗靶点。
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.
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