N-methyladenosine reader YTHDF1 regulates the proliferation and migration of airway smooth muscle cells through mA/cyclin D1 in asthma.

Asthma is a chronic inflammatory respiratory disease, which is involved in multiple pathologic molecular mechanisms and presents a huge challenge to clinic nursing. Emerging evidence suggests that N-methyladenosine (mA) plays critical roles in respiratory system disease. Thus, present work tried to investigate the functions of mA reader YTHDF 1 in asthma. The results indicated that YTHDF1 significantly upregulated in platelet-derived growth factor (PDGF) induced airway smooth muscle cells (ASMCs). Functionally, overexpression of YTHDF1 promoted the proliferation and migration of ASMCs, while YTHDF1 knockdown repressed the proliferation and migration. Mechanistically, there was a mA modification site on cyclin D1 RNA (CCND1 genome) and YTHDF1 combined with cyclin D1 mRNA, thereby enhancing its mRNA stability via m6A-dependent manner. Collectively, these findings reveal a novel axis of YTHDF1/m6A/cyclin D1 in asthma's airway remodeling, which may provide novel therapeutic strategy for asthma.