%0 Journal Article
%T Identifying quantitative sncRNAs signature using global sequencing as a potential biomarker for tuberculosis diagnosis and their role in regulating host response.
%A Kaul S
%A Nair V
%A Gcanga L
%A Lakshmanan V
%A Kalamuddin M
%A Anang V
%A Rathore S
%A Dhawan S
%A Alam T
%A Khanna V
%A Lohiya S
%A Ali S
%A Mannan S
%A Rade K
%A Parihar SP
%A Khanna A
%A Malhotra P
%A Brombacher F
%A Dasaradhi PV
%A Guler R
%A Mohmmed A
%J Int J Biol Macromol
%V 271
%N 0
%D 2024 Jun 28
%M 38815937
%F 8.025
%R 10.1016/j.ijbiomac.2024.132714
%X <B>OBJECTIVE: </B>The study aimed to identify a quantitative signature of circulating small non-coding RNAs (sncRNAs) as a biomarker for pulmonary tuberculosis disease (active-TB/ATB) and explore their regulatory roles in host-pathogen interactions and disease progression.<BR><B>METHODS: </B>We conducted a cross-sectional study recruiting subjects diagnosed with active-TB (drug-sensitive and drug-resistant) and healthy controls. Sera samples were collected and utilized for preparing small RNA libraries. Quantitative patterns of circulating sncRNAs (miRNAs, piRNAs and tRFs) were identified via high-throughput sequencing and DeSeq2 analysis and validated in independent active-TB cohorts. Functional knockdown for two selected miRNAs were also performed.<BR><B>RESULTS: </B>A diagnostic signature of four sncRNAs for both drug-sensitive and drug-resistant active-TB cases was validated, exhibiting an AUC of 0.96 (95% CI: 0.937-0.996, p < 0.001) with 86.7% sensitivity (95% CI: 0.775-0.932) and 91.7% specificity (95% CI: 0.730-0.990) in ROC analysis. Functional knockdown demonstrated regulatory roles of hsa-miR-223-5p and hsa-miR-10b-5p in Mycobacterium tuberculosis (Mtb) growth and pro-inflammatory cytokine expression (IL-6 and IL-8).<BR><B>CONCLUSIONS: </B>The study identified a diagnostic tool utilizing a signature of four sncRNAs with high specificity and sensitivity, enhancing our understanding of sncRNAs as ATB diagnostic biomarker. Additionally, hsa-miR-223-5p and hsa-miR-10b-5p demonstrated potential roles in Mtb pathogenesis and host-response to infection.