School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
Infectious Diseases Unit, Azienda Socio Sanitaria Territoriale di Monza, San Gerardo Hospital, 20900 Monza, Italy.
Int J Mol Sci. 2022 Mar 23;23(7):3486. doi: 10.3390/ijms23073486.
Combined AntiRetroviral Treatments (cARTs) used for HIV infection may result in varied metabolic complications, which in some cases, may be related to patient genetic factors, particularly microRNAs. The use of monozygotic twins, differing only for HIV infection, presents a unique and powerful model for the controlled analysis of potential alterations of miRNAs regulation consequent to cART treatment. Profiling of 2578 mature miRNA in the subcutaneous (SC) adipose tissue and plasma of monozygotic twins was investigated by the GeneChip® miRNA 4.1 array. Real-time PCR and ddPCR experiments were performed in order to validate differentially expressed miRNAs. Target genes of deregulated miRNAs were predicted by the miRDB database (prediction score > 70) and enrichment analysis was carried out with g:Profiler. Processes in SC adipose tissue most greatly affected by miRNA up-regulation included (i) macromolecular metabolic processes, (ii) regulation of neurogenesis, and (iii) protein phosphorylation. Furthermore, KEGG analysis revealed miRNA up-regulation involvement in (i) insulin signaling pathways, (ii) neurotrophin signaling pathways, and (iii) pancreatic cancer. By contrast, miRNA up-regulation in plasma was involved in (i) melanoma, (ii) p53 signaling pathways, and (iii) focal adhesion. Our findings suggest a mechanism that may increase the predisposition of HIV+ patients to insulin resistance and cancer.
联合抗逆转录病毒治疗（cART）用于治疗 HIV 感染可能会导致各种代谢并发症，在某些情况下，这些并发症可能与患者的遗传因素有关，特别是 microRNA。使用仅感染 HIV 不同的同卵双胞胎，为潜在的 miRNA 调控改变的对照分析提供了一个独特而有力的模型。通过 GeneChip® miRNA 4.1 阵列对同卵双胞胎的皮下（SC）脂肪组织和血浆中的 2578 个成熟 miRNA 进行了分析。通过实时 PCR 和 ddPCR 实验对差异表达的 miRNA 进行了验证。通过 miRDB 数据库（预测评分>70）预测了失调 miRNA 的靶基因，并通过 g:Profiler 进行了富集分析。miRNA 上调在 SC 脂肪组织中影响最大的过程包括：（i）大分子代谢过程，（ii）神经发生的调节，和（iii）蛋白质磷酸化。此外，KEGG 分析表明，miRNA 上调参与了（i）胰岛素信号通路，（ii）神经生长因子信号通路，和（iii）胰腺癌。相反，血浆中 miRNA 的上调与（i）黑色素瘤，（ii）p53 信号通路，和（iii）焦点粘连有关。我们的研究结果表明，这种机制可能会增加 HIV+患者对胰岛素抵抗和癌症的易感性。
