MicroRNA Signature of Cigarette Smoking and Evidence for a Putative Causal Role of MicroRNAs in Smoking-Related Inflammation and Target Organ Damage

Abstract

Background Cigarette smoking increases risk for multiple diseases. MicroRNAs (miRNAs) regulate gene expression and may play a role in smoking-induced target organ damage. We sought to describe a miRNA signature of cigarette smoking and relate it to smoking-associated clinical phenotypes, gene expression, and lung inflammatory signaling. Methods and Results Expression profiling of 283 miRNAs was conducted on whole blood-derived RNA from 5,023 Framingham Heart Study participants (54.0% women, mean age 55±13 years) using TaqMan assays and high-throughput RT-qPCR. Associations of miRNA expression with smoking status and associations of smoking-related miRNAs with inflammatory biomarkers and pulmonary function were tested with linear mixed-effects models. We identified a six-miRNA signature of smoking. Five of the six smoking-related miRNAs were associated with serum levels of C-reactive protein or interleukin-6; miR-1180 was associated with pulmonary function measures at a marginally significant level. Bioinformatic evaluation of smoking-associated genes coexpressed with the miRNA signature of cigarette smoking revealed enrichment for immune-related pathways. Smoking-associated miRNAs altered expression of select inflammatory mediators in cell culture gain-of-function assays. Conclusions We characterized a novel miRNA signature of cigarette smoking. The top miRNAs were associated with systemic inflammatory markers and reduced pulmonary function, correlated with expression of genes involved in immune function, and were sufficient to modulate inflammatory signaling. Our results highlight smoking-associated miRNAs and are consistent with the hypothesis that smoking-associated miRNAs serve as mediators of smoking-induced inflammation and target organ damage. These findings call for further mechanistic studies to explore the diagnostic and therapeutic utility of smoking-related miRNAs.

Altered erythroid‐related miRNA levels as a possible novel biomarker for detection of autologous blood transfusion misuse in sport

“…Moreover, all the recruited athletes presented similar performance‐related parameters as directly measured by maximal oxygen consumption (53 ± 9 vs. 57 ± 6 mL/kg/min), weekly training hours (7 ± 1 vs. 9 ± 4), and sport vintage (12 ± 6 vs. 15 ± 6). As microRNA parameters might change after smoking‐related inflammation, only non‐smoker subjects were included in this analysis.…”

Microarray Profiling of Circular RNA Identifies hsa_circ_0126991 as a Potential Risk Factor for Essential Hypertension

“…It is plausible that differences in noncoding RNA may be a result of this change. Willinger et al [2017] reported that 6 microRNAs (miR-1180, miR181a-2-3p, miR-423-5p, miR-25-5p, miR-1285-3p, miR-342-5p) were significantly related to a three-level smoking status, and they further found that these miRNAs have negative associations with the serum concentration of C reactive protein. Interestingly, in the cancer study, tobacco-dysregulated noncoding RNAs were related to clinical characteristics in head and neck squamous cell carcinoma.…”

Environmental Influencers, MicroRNA, and Multiple Sclerosis

“…The miRNA dysregulation has been linked to EBV infection and cigarette smoking in several studies, while vitamin D supplementation was found to regulate the miRNA populations. [108][109][110][111][112][113][114][115][116][117][118][119][120][121][122] MS has been associated with many dysregulated miRNAs with disease modulating effects. 111,117,[123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140] Finding the link between these two groups, environmental factors and miRNAs, may explain the risk of environmental factors on MS pathogenicity.…”

“…161 Smoking is also implicated in the upregulation of miR-342, which is known to distinguish RRMS and progressive MS from controls and RRMS from progressive MS (Tables 1 and 2). 118,127 miR-342 has been shown to promote inflammatory activation of MØ. 118 Interestingly, this miRNA can target several genes, including TNFRSF6B, TRAF3, and KIF21B, which was proved to pose a risk towards MS in the IMSGC study (Table 3).…”