miR-185 and miR-29a are similarly expressed in the bronchoalveolar lavage cells in IPF and lung cancer but common targets DNMT1 and COL1A1 show disease specific patterns

Abstract

Idiopathic pulmonary fibrosis (IPF) and lung cancer (LC) constitute two progressively devastating lung diseases with common risk factors including aging and smoking. There is an increasing interest in the investigation of common pathogenic mechanisms between IPF and LC with therapeutic implications. Several oncomirs, microRNAs associated with malignancy, are also linked with IPF. miR-29a and miR-185 downregulation is probably involved both in carcinogenesis and fibrogenesis. We have previously observed miR-29a and miR-185 downregulation in IPF cells from bronchoalveolar lavage (BAL) and in this study we investigated their expression in LC BAL cells. Common targets of miR-29a and miR-185 such as DNA methyltransferase (DNMT)1, DNMT3b, COL1A1, AKT1 and AKT2 were measured. Potential correlations with pulmonary function tests, smoking status and endobronchial findings were investigated. Similar levels of miR-29a and miR-185 were detected in IPF and LC while their common targets AKT1 and DNMT3b were not found to differ, suggesting potential pathogenetic similarities at the level of key epigenetic regulators. By conrast, COL1A1 mRNA levels were increased in IPF suggesting a disease-specific mRNA signature. Notably, DNMT1 was downregulated in the LC group and its expression was further reduced in the presence of increasing malignant burden as it was implied by the endobronchial findings.

Intriguing Relationships Between Cancer and Systemic Sclerosis: Role of the Immune System and Other Contributors

“…Indeed, the expression of miR-29a is reduced both in fibroblasts and skin in SSc (99, 100), and its overexpression induced a reduction of fibroblast proliferation and collagen synthesis in vitro (101). A similar reduced expression of miR-29a has also been found both in broncho-alveolar cells from IPF and lung cancer patients, suggesting a common link between the two conditions (102). Altogether, miR-21 and miR-29 family members exhibit synergistic functions to modulate fibroblast fate both in healthy and fibrotic conditions.…”

Akt1 and Akt2 Isoforms Play Distinct Roles in Regulating the Development of Inflammation and Fibrosis Associated with Alcoholic Liver Disease

“…Blocking of both Akt1 and Akt2 reversed the effect, both in culture and in the EBL mouse model, suggesting that both isoforms play an active role in fibrogenesis. This is consistent with results from Bibaki et al, which demonstrated that miR-29a, miR-185, and their targets Akt1 and Akt2, were involved in the development of idiopathic pulmonary fibrosis and lung cancer [53]. However, Lan et al showed that only Akt2 was involved in renal fibrosis [54].…”

Scar tissue to lung cancer; pathways and treatment

“…On the other hand COL1A1 mRNA levels were increased in interstitial pulmonary fibrosis suggesting a disease‑specific mRNA signature. DNMT1 was downregulated in the lung cancer group and its expression was further reduced in the presence of increasing malignant burden as it was implied by the endobronchial findings 54. The expression levels of FGF2 mRNA and protein in the non-small cell LC tissues were significantly higher than those in the adjacent normal tissues (P<0.001).…”