AFAP1-AS1 induces cisplatin resistance in non-small cell lung cancer through PI3K/AKT pathway

Cisplatin (DDP)-resistance in non-small cell lung carcinoma (NSCLC) severely influences the prognosis of affected patients. This study aims to uncover the potential role of AFAP1-AS1 in DDP-resistant NSCLC and the underlying mechanism. The expression level of AFAP1-AS1 in DDP-resistant NSCLC patients and DDP-resistant A549 cells (A549/DDP) was determined. Proliferative, cell cycle distribution, apoptotic, migratory and invasive changes in A549/DDP cells transfected with si-AFAP1-AS1 were assessed. Western blot analyses were conducted to examine the protein levels of phosphorylated protein kinase B (p-AKT), AKT, E-cadherin, N-cadherin, vimentin and snail in A549/DDP cells. Furthermore, the ubcellular distribution of AFAP1-AS1 was analyzed. Through RNA immunoprecipitation (RIP) assay, the interaction between AFAP1-AS1 and enhancer of zeste homolog 2 (EZH2) was explored. Finally, the regulatory effect of EZH2 on the PI3K/AKT pathway was investigated by western blot analysis. AFAP1-AS1 was upregulated in DDP-resistant NSCLC patients and A549/DDP cells. Transfection with si-AFAP1-AS1 attenuated the proliferative, migratory and invasive abilities, arrested cell cycle in G0/G1 phase, and stimulated apoptosis of A549/DDP cells. Silencing of AFAP1-AS1 upregulated E-cadherin and downregulated N-cadherin, vimentin and snail expression levels. Furthermore, AFAP1-AS1 was verified to interact with EZH2. The relative expression of EZH2 was reduced by transfection of A549/DDP cells with si-AFAP1-AS1. Silencing of EZH2 inhibited the activation of PI3K/AKT pathway. In conclusion, AFAP1-AS1 accelerates the proliferative and metastatic abilities of A549/DDP cells, whereas inhibits the apoptosis of A549/DDP cells, by interacting with EZH2 to activate the PI3K/AKT pathway; thus, inducing DDP resistance in NSCLC.