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Exosomal microRNAs are novel circulating biomarkers in cigarette, waterpipe smokers, E-cigarette users and dual smokers.
BMC Med Genomics. 2020 09 10; 13(1):128.BM

Abstract

BACKGROUND

Electronic cigarettes (e-cigs) vaping, cigarette smoke, and waterpipe tobacco smoking are associated with various cardiopulmonary diseases. microRNAs are present in higher concentration in exosomes that play an important role in various physiological and pathological functions. We hypothesized that the non-coding RNAs transcript may serve as susceptibility to disease biomarkers by smoking and vaping.

METHODS

Plasma exosomes/EVs from cigarette smokers, waterpipe smokers and dual smokers (cigarette and waterpipe) were characterized for their size, morphology and TEM, Nanosight and immunoblot analysis. Exosomal RNA was used for small RNA library preparation and the library was quantified using the High Sensitivity DNA Analysis on the Agilent 2100 Bioanalyzer system and sequenced using the Illumina NextSeq 500 and were converted to fastq format for mapping genes.

RESULTS

Enrichment of various non-coding RNAs that include microRNAs, tRNAs, piRNAs, snoRNAs, snRNAs, Mt-tRNAs, and other biotypes are shown in exosomes. A comprehensive differential expression analysis of miRNAs, tRNAs and piRNAs showed significant changes across different pairwise comparisons. The seven microRNAs that were common and differentially expressed of when all the smoking and vaping groups were compared with non-smokers (NS) are hsa-let-7a-5p, hsa-miR-21-5p, hsa-miR-29b-3p, hsa-let-7f-5p, hsa-miR-143-3p, hsa-miR-30a-5p and hsa-let-7i-5p. The e-cig vs. NS group has differentially expressed 5 microRNAs (hsa-miR-224-5p, hsa-miR-193b-3p, hsa-miR-30e-5p, hsa-miR-423-3p, hsa-miR-365a-3p, and hsa-miR-365b-3p), which are not expressed in other three groups. Gene set enrichment analysis of microRNAs showed significant changes in the top six enriched functions that consisted of biological pathway, biological process, molecular function, cellular component, site of expression and transcription factor in all the groups. Further, the pairwise comparison of tRNAs and piRNA in all these groups revealed significant changes in their expressions.

CONCLUSIONS

Plasma exosomes of cigarette smokers, waterpipe smokers, e-cig users and dual smokers have common differential expression of microRNAs which may serve to distinguish smoking and vaping subjects from NS. Among them has-let-7a-5p has high sensitivity and specificity to distinguish NS with the rest of the users, using ROC curve analysis. These findings will pave the way for the utilizing the potential of exosomes/miRNAs as a novel theranostic agents in lung injury and disease caused by tobacco smoking and vaping.

Links

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Authors+Show Affiliations

Singh KP
Department of Environmental Medicine, University of Rochester Medical Center, Box 850, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
Maremanda KP
Department of Environmental Medicine, University of Rochester Medical Center, Box 850, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
Li D
Department of Clinical & Translational Research, University of Rochester Medical Center, Rochester, NY, USA.
Rahman I
Department of Environmental Medicine, University of Rochester Medical Center, Box 850, 601 Elmwood Avenue, Rochester, NY, 14642, USA. irfan_rahman@urmc.rochester.edu.

MeSH

BiomarkersCase-Control StudiesElectronic Nicotine Delivery SystemsExosomesGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksHumansMicroRNAsROC CurveSmokersTobacco SmokingWater Pipe Smoking

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

32912198

Citation

Singh, Kameshwar P., et al. "Exosomal microRNAs Are Novel Circulating Biomarkers in Cigarette, Waterpipe Smokers, E-cigarette Users and Dual Smokers." BMC Medical Genomics, vol. 13, no. 1, 2020, p. 128.
Singh KP, Maremanda KP, Li D, et al. Exosomal microRNAs are novel circulating biomarkers in cigarette, waterpipe smokers, E-cigarette users and dual smokers. BMC Med Genomics. 2020;13(1):128.
Singh, K. P., Maremanda, K. P., Li, D., & Rahman, I. (2020). Exosomal microRNAs are novel circulating biomarkers in cigarette, waterpipe smokers, E-cigarette users and dual smokers. BMC Medical Genomics, 13(1), 128. https://doi.org/10.1186/s12920-020-00748-3
Singh KP, et al. Exosomal microRNAs Are Novel Circulating Biomarkers in Cigarette, Waterpipe Smokers, E-cigarette Users and Dual Smokers. BMC Med Genomics. 2020 09 10;13(1):128. PubMed PMID: 32912198.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exosomal microRNAs are novel circulating biomarkers in cigarette, waterpipe smokers, E-cigarette users and dual smokers. AU - Singh,Kameshwar P, AU - Maremanda,Krishna P, AU - Li,Dongmei, AU - Rahman,Irfan, Y1 - 2020/09/10/ PY - 2020/01/28/received PY - 2020/06/25/accepted PY - 2020/9/11/entrez PY - 2020/9/12/pubmed PY - 2021/5/11/medline KW - Cigarette smokers KW - E-cig users KW - Exosomes KW - Extracellular vesicles KW - Plasma KW - Waterpipe smokers KW - microRNA SP - 128 EP - 128 JF - BMC medical genomics JO - BMC Med Genomics VL - 13 IS - 1 N2 - BACKGROUND: Electronic cigarettes (e-cigs) vaping, cigarette smoke, and waterpipe tobacco smoking are associated with various cardiopulmonary diseases. microRNAs are present in higher concentration in exosomes that play an important role in various physiological and pathological functions. We hypothesized that the non-coding RNAs transcript may serve as susceptibility to disease biomarkers by smoking and vaping. METHODS: Plasma exosomes/EVs from cigarette smokers, waterpipe smokers and dual smokers (cigarette and waterpipe) were characterized for their size, morphology and TEM, Nanosight and immunoblot analysis. Exosomal RNA was used for small RNA library preparation and the library was quantified using the High Sensitivity DNA Analysis on the Agilent 2100 Bioanalyzer system and sequenced using the Illumina NextSeq 500 and were converted to fastq format for mapping genes. RESULTS: Enrichment of various non-coding RNAs that include microRNAs, tRNAs, piRNAs, snoRNAs, snRNAs, Mt-tRNAs, and other biotypes are shown in exosomes. A comprehensive differential expression analysis of miRNAs, tRNAs and piRNAs showed significant changes across different pairwise comparisons. The seven microRNAs that were common and differentially expressed of when all the smoking and vaping groups were compared with non-smokers (NS) are hsa-let-7a-5p, hsa-miR-21-5p, hsa-miR-29b-3p, hsa-let-7f-5p, hsa-miR-143-3p, hsa-miR-30a-5p and hsa-let-7i-5p. The e-cig vs. NS group has differentially expressed 5 microRNAs (hsa-miR-224-5p, hsa-miR-193b-3p, hsa-miR-30e-5p, hsa-miR-423-3p, hsa-miR-365a-3p, and hsa-miR-365b-3p), which are not expressed in other three groups. Gene set enrichment analysis of microRNAs showed significant changes in the top six enriched functions that consisted of biological pathway, biological process, molecular function, cellular component, site of expression and transcription factor in all the groups. Further, the pairwise comparison of tRNAs and piRNA in all these groups revealed significant changes in their expressions. CONCLUSIONS: Plasma exosomes of cigarette smokers, waterpipe smokers, e-cig users and dual smokers have common differential expression of microRNAs which may serve to distinguish smoking and vaping subjects from NS. Among them has-let-7a-5p has high sensitivity and specificity to distinguish NS with the rest of the users, using ROC curve analysis. These findings will pave the way for the utilizing the potential of exosomes/miRNAs as a novel theranostic agents in lung injury and disease caused by tobacco smoking and vaping. SN - 1755-8794 UR - https://www.unboundmedicine.com/medline/citation/32912198/Exosomal_microRNAs_are_novel_circulating_biomarkers_in_cigarette_waterpipe_smokers_E_cigarette_users_and_dual_smokers_ DB - PRIME DP - Unbound Medicine ER -