Cyclophilin A regulates A549 cells apoptosis via stabilizing Twist1 protein.

Cyclophilin A (CypA) is an essential member of the immunophilin family. As an intracellular target of immunosuppressive drug cyclosporin A (CsA) or a peptidyl-prolyl cis/trans isomerase (PPIase), it catalyzes the cis-trans isomerization of proline amidic peptide bonds, through which, it regulates a variety of biological processes, such as intracellular signaling, transcription, and apoptosis. In this study, we found that intracellular CypA enhanced Twist1 phosphorylation at Ser68 and inhibited apoptosis in A549 cells. Mechanistically, CypA could mediate the phosphorylation of Twist1 at Ser68 via p38 MAPK, which inhibited its ubiquitination-mediated degradation. In addition, CypA increased Twist-p65 interaction and nuclear accumulation, which regulated Twist1-dependent expression of CDH1 and CDH2. Our findings collectively indicated the role of CypA in Twist1-mediated A549 cells apoptosis through stabilizing Twist1 protein.