Smoking-related microRNAs and mRNAs in human peripheral blood mononuclear cells.
Teenager smoking is of great importance in public health. Functional roles of microRNAs have been documented in smoke-induced gene expression changes, but comprehensive mechanisms of microRNA-mRNA regulation and benefits remained poorly understood. We conducted the Teenager Smoking Reduction Trial (TSRT) to investigate the causal association between active smoking reduction and whole-genome microRNA and mRNA expression changes in human peripheral blood mononuclear cells (PBMC). A total of 12 teenagers with a substantial reduction in smoke quantity and a decrease in urine cotinine/creatinine ratio were enrolled in genomic analyses. In Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA), differentially expressed genes altered by smoke reduction were mainly associated with glucocorticoid receptor signaling pathway. The integrative analysis of microRNA and mRNA found eleven differentially expressed microRNAs negatively correlated with predicted target genes. CD83 molecule regulated by miR-4498 in human PBMC, was critical for the canonical pathway of communication between innate and adaptive immune cells. Our data demonstrated that microRNAs could regulate immune responses in human PBMC after habitual smokers quit smoking and support the potential translational value of microRNAs in regulating disease-relevant gene expression caused by tobacco smoke.
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Ming-Wei
MW
Su
Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Sung-Liang
SL
Yu
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Wen-Chang
WC
Lin
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Ching-Hui
CH
Tsai
School of Medicine, National Taiwan University, Taipei, Taiwan.
Po-Hua
PH
Chen
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address: leolee@ntu.edu.tw.
Yungling Leo
YL
Lee
D000293:Adolescent; D002648:Child; D003367:Cotinine / Q000652:urine; D003404:Creatinine / Q000652:urine; D005260:Female; D005541:Forced Expiratory Volume; D063990:Gene Ontology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012907:Smoking / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000652:urine; D014797:Vital Capacity
D035683:MicroRNAs; D012333:RNA, Messenger; D003404:Creatinine; D003367:Cotinine
Integrative analysis; Smoke reduction; mRNA; microRNA