Reid Victoria A, Ramos Enrique I, Veerapandian Raja, Carmona Areanna, Gadad Shrikanth S, Dhandayuthapani Subramanian
Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA.
Center of Emphasis in Cancer, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA.
Noncoding RNA. 2024 Jul 13;10(4):40. doi: 10.3390/ncrna10040040.
Tuberculosis (TB) is the leading cause of death among people with HIV-1 infection. To improve the diagnosis and treatment of HIV-TB patients, it is important to understand the mechanisms underlying these conditions. Here, we used an integrated genomics approach to analyze and determine the lncRNAs that are dysregulated in HIV-TB patients and HIV-TB patients undergoing anti-retroviral therapy (ART) using a dataset available in the public domain. The analyses focused on the portion of the genome transcribed into non-coding transcripts, which historically have been poorly studied and received less focus. This revealed that Mtb infection in HIV prominently up-regulates the expression of long non-coding RNA (lncRNA) genes , , , , and and down-regulates the expression of lncRNAs , , , , and . It also revealed that ART down-regulates the expression of some lncRNA genes (, , , and ) that are highly up-regulated in HIV-TB patients. Furthermore, the interrogation of the genomic regions that are associated with regulated lncRNAs showed enrichment for biological processes linked to immune pathways in TB-infected conditions. However, intriguingly, TB patients treated with ART showed completely opposite and non-overlapping pathways. Our findings suggest that lncRNAs could be used to identify critical diagnostic, prognostic, and treatment targets for HIV-TB patients.
结核病（TB）是HIV-1感染者的主要死因。为了改善HIV-TB患者的诊断和治疗，了解这些疾病背后的机制很重要。在此，我们使用综合基因组学方法，利用公开领域可用的数据集，分析并确定在HIV-TB患者以及接受抗逆转录病毒治疗（ART）的HIV-TB患者中失调的长链非编码RNA（lncRNA）。分析集中于基因组转录为非编码转录本的部分，这部分在历史上研究较少且关注度较低。结果显示，HIV感染者中的结核分枝杆菌（Mtb）感染显著上调长链非编码RNA（lncRNA）基因、、、、和的表达，并下调lncRNAs、、、、和的表达。研究还表明，ART下调了一些在HIV-TB患者中高度上调的lncRNA基因（、、、和）的表达。此外，对与受调控lncRNAs相关的基因组区域的研究表明，在结核感染情况下，与免疫途径相关的生物学过程出现富集。然而，有趣的是，接受ART治疗的TB患者表现出完全相反且不重叠的途径。我们的研究结果表明，lncRNAs可用于识别HIV-TB患者的关键诊断、预后和治疗靶点。
