Long non-coding RNA expression in PBMCs of patients with active pulmonary tuberculosis

Guoli Li; Zhelong Feng; Honghuan Song; Yajing Wang; Limei Zhu; Yan Li

doi:10.3389/fmicb.2023.1257267

Long non-coding RNA expression in PBMCs of patients with active pulmonary tuberculosis

Front Microbiol. 2023 Dec 14:14:1257267. doi: 10.3389/fmicb.2023.1257267. eCollection 2023.

Authors

Guoli Li^#¹, Zhelong Feng^#², Honghuan Song¹, Yajing Wang², Limei Zhu¹, Yan Li^{3

1}

Affiliations

¹ Department of Chronic Communicable Disease, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.
² School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
³ Integrated Service and Management Office, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.

^# Contributed equally.

Abstract

Purpose: Mycobacterium tuberculosis (Mtb) infection is the primary cause of the chronic infectious illness tuberculosis (TB). Long non-coding RNAs (lncRNAs) are functional RNA molecules that cannot be translated into proteins and play a crucial role in regulating the immune system's innate and adaptive responses. It has been demonstrated that the dysregulation of lncRNA expression is associated with various human diseases. However, the mechanism underlying the involvement of so many lncRNAs in the immune response to TB infection remains unclear. The objective of our current study was to identify a number of significantly differentially expressed lncRNAs in peripheral blood mononuclear cells (PBMCs) from TB patients and to select the most indicative lncRNAs as potential biomarkers for active pulmonary tuberculosis.

Methods: Microarray analysis was performed to determine the lncRNA and mRNA expression profiles in TB patients using a case-control model. The differentially expressed lncRNAs were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to investigate potential roles and pathways associated with the pathogenesis of TB infection, and to screen lncRNAs specifically linked to TB infection. Using real-time fluorescence quantitative PCR (QRT-PCR), specific lncRNAs were identified in TB patients and latent infections.

Results: Our findings revealed that various signaling pathways were differentially expressed in TB-infected individuals, suggesting a potential role for lncRNAs in the immunological responses driven by TB infection. This study provides crucial guidelines for future functional research. Upregulated lncRNAs were mainly enriched in Neutrophil extracellular trap formation and Chemokine signaling pathways, while downregulated lncRNAs were enriched in Neuroactive ligand-receptor interaction and Cushing syndrome in TB PBMCs. Furthermore, we found that lnc-XPNPEP1-5, lnc-CASKIN2-2, lnc-HSPA13-6, lnc-CLIC5-1, and LINC02502 were significantly downregulated in TB-infected patients, while LINC00528, lnc-SLC45A4-3, and LINC00926 were significantly upregulated in TB patients and latent infections. These eight lncRNAs, identified as novel biological marker candidates for diagnosing TB infection, were validated by real-time fluorescence quantitative PCR (QRT-PCR).

Conclusion: The abnormally expressed lncRNAs identified in this research may provide crucial information for understanding the pathophysiological characteristics of TB patients and the dysfunction of PBMCs. Our findings reveal potential targets for early TB diagnosis and therapy, as well as offer new insights into the mechanisms underlying TB infection.

Keywords: PBMCs; RRT-PCR; biomarker; latent tuberculosis infection (LTBI); long non-coding RNAs; tuberculosis.

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China Youth Science Foundation Project (grant numbers 8130144 and 81302480), Jiangsu Provincial Medical Key Discipline (ZDXK202250) and Jiangsu Young Medical Talents Project (grant number QNRC2016541). The funding sources had no input into the planning of the study, gathering and analyzing the data, choosing to publish, or writing the manuscript.