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Current Smoking is Associated with Decreased Expression of miR-335-5p in Parenchymal Lung Fibroblasts

Ong, J., van den Berg, A., Faiz, A., Boudewijn, I. M., Timens, W., Vermeulen, C. J., Oliver, B. G., Kok, K., Terpstra, M. M., van den Berge, M., Brandsma, C-A. & Kluiver, J., 2-Oct-2019, In : International Journal of Molecular Sciences. 20, 20, 14 p., 5176.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number5176
Number of pages14
JournalInternational Journal of Molecular Sciences
Volume20
Issue number20
Publication statusPublished - 2-Oct-2019

    Keywords

  • miRNAs, lung fibroblasts, smoking status, regional methylation, BREAST-CANCER CELLS, CIGARETTE-SMOKE, TUMOR-SUPPRESSOR, MESENCHYMAL TRANSITION, OXIDATIVE STRESS, GASTRIC-CANCER, UP-REGULATION, PROLIFERATION, INVASION, METASTASIS

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