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

Liu,Yang; Hu,Qiang; Wang,Xihui

doi:10.3892/ol.2019.11175

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

Authors:
- Yang Liu
- Qiang Hu
- Xihui Wang
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Affiliations: Department of Pharmacy, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China, Department of Radiology, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China, Department of Blood Transfusion, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China
Published online on: December 2, 2019 https://doi.org/10.3892/ol.2019.11175
Pages: 1024-1030
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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