1. Current Smoking is Associated with Decreased Expression of miR-335-5p in Parenchymal Lung Fibroblasts
- Author
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Klaas Kok, Jennie Ong, Brian G. Oliver, Cornelis J. Vermeulen, Maarten van den Berge, Wim Timens, Joost Kluiver, Anke van den Berg, Alen Faiz, Corry-Anke Brandsma, Ilse M. Boudewijn, Martijn Terpstra, Stem Cell Aging Leukemia and Lymphoma (SALL), Translational Immunology Groningen (TRIGR), Groningen Research Institute for Asthma and COPD (GRIAC), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
Male ,INVASION ,UP-REGULATION ,Metastasis ,lcsh:Chemistry ,0302 clinical medicine ,TUMOR-SUPPRESSOR ,OXIDATIVE STRESS ,lcsh:QH301-705.5 ,Lung ,Spectroscopy ,Cells, Cultured ,0303 health sciences ,Smokers ,Smoking ,PROLIFERATION ,BREAST-CANCER CELLS ,General Medicine ,Methylation ,respiratory system ,regional methylation ,3. Good health ,Computer Science Applications ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,miRNAs ,Female ,RNA Interference ,medicine.symptom ,Inflammation ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Downregulation and upregulation ,microRNA ,Parenchyma ,medicine ,Humans ,RNA, Messenger ,Physical and Theoretical Chemistry ,Fibroblast ,Molecular Biology ,030304 developmental biology ,MESENCHYMAL TRANSITION ,Chemical Physics ,business.industry ,Gene Expression Profiling ,Organic Chemistry ,lung fibroblasts ,DNA Methylation ,Fibroblasts ,medicine.disease ,respiratory tract diseases ,MicroRNAs ,lcsh:Biology (General) ,lcsh:QD1-999 ,Gene Expression Regulation ,CIGARETTE-SMOKE ,METASTASIS ,Cancer research ,business ,GASTRIC-CANCER ,Biomarkers ,smoking status - Abstract
Cigarette smoking causes lung inflammation and tissue damage. Lung fibroblasts play a major role in tissue repair. Previous studies have reported smoking-associated changes in fibroblast responses and methylation patterns. Our aim was to identify the effect of current smoking on miRNA expression in primary lung fibroblasts. Small RNA sequencing was performed on lung fibroblasts from nine current and six ex-smokers with normal lung function. MiR-335-5p and miR-335-3p were significantly downregulated in lung fibroblasts from current compared to ex-smokers (false discovery rate (FDR) <, 0.05). Differential miR-335-5p expression was validated with RT-qPCR (p-value = 0.01). The results were validated in lung tissue from current and ex-smokers and in bronchial biopsies from non-diseased smokers and never-smokers (p-value <, 0.05). The methylation pattern of the miR-335 host gene, determined by methylation-specific qPCR, did not differ between current and ex-smokers. To obtain insights into the genes regulated by miR-335-5p in fibroblasts, we overlapped all proven miR-335-5p targets with our previously published miRNA targetome data in lung fibroblasts. This revealed Rb1, CARF, and SGK3 as likely targets of miR-335-5p in lung fibroblasts. Our study indicates that miR-335-5p downregulation due to current smoking may affect its function in lung fibroblasts by targeting Rb1, CARF and SGK3.
- Published
- 2019