Infection and Drug Resistance (Jul 2018)

Identifying differentially expressed long non-coding RNAs in PBMCs in response to the infection of multidrug-resistant tuberculosis

  • Yan H,
  • Xu R,
  • Zhang XR,
  • Wang Q,
  • Pang J,
  • Zhang X,
  • Chang X,
  • Zhang Y

Journal volume & issue
Vol. Volume 11
pp. 945 – 959


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Hong Yan,1,* Rufeng Xu,2,* Xiangrong Zhang,3 Qian Wang,1 Jing Pang,2 Xia Zhang,3 Xiaoai Chang,2 Yaqin Zhang2 1Department of Laboratory Medicine, Nanjing Chest Hospital, Nanjing 210029, China; 2Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu 210029, China; 3Nanjing Public Health Clinical Center, Nanjing, Jiangsu 211133,China *These authors contributed equally to this work Purpose: The aim of this paper was to identify differentially expressed long non-coding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMCs) influenced by the infection of multidrug-resistant tuberculosis (MDR-TB). Materials and methods: IncRNA and mRNA expression profiles in PBMCs derived from healthy controls (HCs) and individuals with MDR-TB and drug-sensitive tuberculosis (DS-TB) were analyzed and compared by microarray assay. Six lncRNAs were randomly selected for validation by using real-time quantitative polymerase chain reaction (RT-qPCR). The biological functions and signaling pathways affected by the differentially expressed mRNAs were investigated by using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based approaches. Results: Compared with the HC group, 1,429 lncRNAs (983 mRNAs) and 2,040 lncRNAs (1,407 mRNAs) were identified to be deregulated in the MDR-TB group and in the DS-TB group, respectively, and 1,511 lncRNAs and 1,047 mRNAs were identified to be differentially expressed in both MDR-TB and DS-TB groups. Between the three groups, 22 lncRNAs and 38 mRNAs were found deregulated. Most deregulated lncRNAs were from intergenic regions (~55% of the total), natural antisense to protein-coding loci (~32% of the total), or intronic antisense to protein-coding loci (~5% of the total). Significantly enriched signaling pathways regulated by the deregulated mRNAs were mainly associated with natural killer cell-mediated cytotoxicity, antigen processing and presentation, graft-vs-host disease, the transforming growth factor-β signaling pathway, and the Hippo signaling pathway. Conclusion: This study is the first to report differentially expressed lncRNAs in PBMCs in response to MDR-TB infection. It revealed that some lncRNAs might be associated with regulating host immune response to MDR-TB infection. Further elucidation of the potential of these deregulated lncRNAs in MDR-TB and its reactivation requires further study. Keywords: mycobacterium tuberculosis, MDR, molecular characterization, lncRNA, infection