Long non-coding RNAs ENST00000429730.1 and MSTRG.93125.4 are associated with metabolic activity in tuberculosis lesions of sputum-negative tuberculosis patients

Accurate diagnosis of complete inactivation of tuberculosis lesions is still a challenge with respect to sputum-negative tuberculosis. RNA-sequencing was conducted to uncover potential lncRNA indicators of metabolic activity in tuberculosis lesions. Lung tissues with high metabolic activity and low metabolic activity demonstrated by fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography were collected from five sputum-negative tuberculosis patients for RNA-sequencing. Differentially-expressed mRNAs and lncRNAs were identified. Their correlations were evaluated to construct lncRNA-mRNA co-expression network, in which lncRNAs and mRNAs with high degrees were confirmed by quantitative real-time PCR using samples collected from 11 patients. Prediction efficiencies of lncRNA indicators were assessed by receiver operating characteristic curve analysis. Bioinformatics analysis was performed for potential lncRNAs. 386 mRNAs and 44 lncRNAs were identified to be differentially expressed. Differentially-expressed mRNAs in lncRNA-mRNA co-expression network were significantly associated with fibrillar collagen, platelet-derived growth factor binding, and leukocyte migration involved in inflammatory response. Seven mRNAs (C1QB, CD68, CCL5, CCL19, MMP7, HLA-DMB, and CYBB) and two lncRNAs (ENST00000429730.1 and MSTRG.93125.4) were validated to be significantly up-regulated. The area under the curve of ENST00000429730.1 and MSTRG.93125.4 was 0.750 and 0.813, respectively. Two lncRNAs ENST00000429730.1 and MSTRG.93125.4 might be considered as potential indicators of metabolic activity in tuberculosis lesions for sputum-negative tuberculosis.

[1]  M. Sonego,et al.  Splicing factor proline- and glutamine-rich (SFPQ) protein regulates platinum response in ovarian cancer-modulating SRSF2 activity , 2020, Oncogene.

[2]  K. Ganbarov,et al.  Long non-coding RNA molecules in tuberculosis. , 2020, International journal of biological macromolecules.

[3]  Alimuddin Zumla,et al.  Towards more accurate 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging in Active and Latent Tuberculosis. , 2020, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[4]  K. Natarajan,et al.  Regulation of Interferon-γ receptor (IFN-γR) expression in macrophages during Mycobacterium tuberculosis infection , 2020, Biomolecular concepts.

[5]  Emilia Harding,et al.  WHO global progress report on tuberculosis elimination. , 2019, The Lancet. Respiratory medicine.

[6]  Yong-Xin Cui,et al.  18F-FDG Positron-Emission Tomography/Computed Tomography Findings of Radiographic Lesions Suggesting Old Healed Pulmonary Tuberculosis and High-risk Signs of Predicting Recurrence: A Retrospective Study , 2019, Scientific Reports.

[7]  M. Gaxiola,et al.  Delayed resolution of bleomycin-induced pulmonary fibrosis in absence of MMP13 (collagenase 3). , 2019, American journal of physiology. Lung cellular and molecular physiology.

[8]  Konstantin Nikolaou,et al.  Whole-Body [ 18 F ]-FDG-PET / MRI for Oncology : A Consensus Recommendation * Konsensempfehlungen zur Anwendung der Ganzkörper [ 18 F ]-FDG-PET / MRT in der onkologischen Bildgebung , 2019 .

[9]  I. Lawal,et al.  Monitoring Response to Therapy. , 2017, Seminars in nuclear medicine.

[10]  S. Khader,et al.  Cytokines and Chemokines in Mycobacterium tuberculosis Infection , 2016, Microbiology spectrum.

[11]  Peter J Dodd,et al.  The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling , 2016, PLoS medicine.

[12]  Robert M. DiFazio,et al.  PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis , 2016, PLoS pathogens.

[13]  A. Crook,et al.  Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. , 2014, The New England journal of medicine.

[14]  Hong Ma,et al.  RNA-seq analyses of multiple meristems of soybean: novel and alternative transcripts, evolutionary and functional implications , 2014, BMC Plant Biology.

[15]  T. Shiomi,et al.  MMP-1 drives immunopathology in human tuberculosis and transgenic mice. , 2011, The Journal of clinical investigation.

[16]  Xavier Robin,et al.  pROC: an open-source package for R and S+ to analyze and compare ROC curves , 2011, BMC Bioinformatics.

[17]  J. Casanova,et al.  Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease , 2011, Nature Immunology.

[18]  Shuli Kang,et al.  Large-scale prediction of long non-coding RNA functions in a coding–non-coding gene co-expression network , 2011, Nucleic acids research.

[19]  G. Beamer,et al.  CCL5 participates in early protection against Mycobacterium tuberculosis , 2010, Journal of leukocyte biology.

[20]  L. Bermudez,et al.  Secreted Mycobacterium tuberculosis Rv3654c and Rv3655c Proteins Participate in the Suppression of Macrophage Apoptosis , 2010, PloS one.

[21]  Bruno Jedynak,et al.  Noninvasive Pulmonary [18F]-2-Fluoro-Deoxy-d-Glucose Positron Emission Tomography Correlates with Bactericidal Activity of Tuberculosis Drug Treatment , 2009, Antimicrobial Agents and Chemotherapy.

[22]  Andrew J. Ewald,et al.  Matrix metalloproteinases and the regulation of tissue remodelling , 2007, Nature Reviews Molecular Cell Biology.

[23]  Y. Xu,et al.  RNA-Binding Protein HuR Is Required for Stabilization of SLC11A1 mRNA and SLC11A1 Protein Expression , 2005, Molecular and Cellular Biology.

[24]  J. Flynn,et al.  CCR5-Deficient Mice Control Mycobacterium tuberculosis Infection despite Increased Pulmonary Lymphocytic Infiltration1 , 2004, The Journal of Immunology.

[25]  R. Horsburgh,et al.  Priorities for the treatment of latent tuberculosis infection in the United States. , 2004, The New England journal of medicine.

[26]  Epco Hasker,et al.  Recurrence in tuberculosis: relapse or reinfection? , 2003, The Lancet. Infectious diseases.

[27]  Kamran Siddiqi,et al.  Clinical diagnosis of smear-negative pulmonary tuberculosis in low-income countries: the current evidence. , 2003, The Lancet. Infectious diseases.

[28]  J. Blackwell,et al.  SLC11A1 (formerly NRAMP1) and disease resistance , 2001, Cellular microbiology.

[29]  D. Glidden,et al.  Identifying pulmonary tuberculosis in patients with negative sputum smear results. , 2001, Chest.

[30]  J Vandekerckhove,et al.  Nuclear relocalization of the pre-mRNA splicing factor PSF during apoptosis involves hyperphosphorylation, masking of antigenic epitopes, and changes in protein interactions. , 2001, Molecular biology of the cell.

[31]  P. Butcher,et al.  Detection of mRNA Transcripts and Active Transcription in Persistent Mycobacterium tuberculosisInduced by Exposure to Rifampin or Pyrazinamide , 2000, Journal of bacteriology.

[32]  C. Nathan,et al.  Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[33]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[34]  L. Williams,et al.  Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization , 1999, The Journal of experimental medicine.

[35]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[36]  A. Wangoo,et al.  Up‐regulation of alveolar macrophage platelet‐derived growth factor‐B (PDGF‐B) mRNA by interferon‐gamma from Mycobacterium tuberculosis antigen (PPD)‐stimulated lymphocytes , 1993, Clinical and experimental immunology.

[37]  S. Kaufmann,et al.  Mycobacterium tuberculosis triggers formation of lymphoid structure in murine lungs. , 2007, The Journal of infectious diseases.

[38]  Hiroyuki Ogata,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 1999, Nucleic Acids Res..