接受抗逆转录病毒治疗的艾滋病病毒感染者和结核病患者体内 lncRNA 的差异表达

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-Coding RNA Pub Date : 2024-07-13 DOI:10.3390/ncrna10040040

Victoria A. Reid, Enrique I. Ramos, R. Veerapandian, Areanna Carmona, Shrikanth S. Gadad, S. Dhandayuthapani

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引用次数: 0

摘要

结核病（TB）是导致 HIV-1 感染者死亡的主要原因。为了改善 HIV-TB 患者的诊断和治疗，了解这些病症的发病机制非常重要。在这里，我们使用了一种综合基因组学方法，利用公共领域的数据集分析并确定了在HIV-TB患者和接受抗逆转录病毒疗法（ART）的HIV-TB患者中出现失调的lncRNAs。分析的重点是基因组中转录为非编码转录本的部分，对这部分的研究历来较少，关注度也不高。结果发现，HIV 感染 Mtb 后，长非编码 RNA（lncRNA）基因 DAAM2-AS1、COL4A2-AS1、LINC00599、AC008592.1 和 CLRN1-AS1 的表达显著上调，而 lncRNA 基因 AC111000.4、AC100803.3、AC016168.2、AC245100.7 和 LINC02073 的表达则显著下调。研究还发现，抗逆转录病毒疗法会下调一些在 HIV-TB 患者中高度上调的 lncRNA 基因（COL4A2-AS1、AC079210.1、MFA-AS1 和 LINC01993）的表达。此外，对与受调控的 lncRNA 相关的基因组区域进行的分析表明，在结核病感染条件下，与免疫途径相关的生物过程富集。然而，耐人寻味的是，接受抗逆转录病毒疗法治疗的肺结核患者表现出完全相反且不重叠的通路。我们的研究结果表明，lncRNAs 可用于确定 HIV-TB 患者的关键诊断、预后和治疗目标。

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Differential Expression of lncRNAs in HIV Patients with TB and HIV-TB with Anti-Retroviral Treatment

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 DAAM2-AS1, COL4A2-AS1, LINC00599, AC008592.1, and CLRN1-AS1 and down-regulates the expression of lncRNAs AC111000.4, AC100803.3, AC016168.2, AC245100.7, and LINC02073. It also revealed that ART down-regulates the expression of some lncRNA genes (COL4A2-AS1, AC079210.1, MFA-AS1, and LINC01993) 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.

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来源期刊

Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

6.70

自引率

4.70%

发文量

审稿时长

10 weeks

期刊介绍： Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.