Lung adenocarcinoma (LUAD) is one of the primary culprits of cancer-related deaths. Current treatment modalities for LUAD have certain limitations, necessitating innovating effective LUAD treatment strategies. Prostaglandin E synthase (PTGES) and TF activating protein 2C (TFAP2C) in the process of drug resistance in LUAD are less studied and need further in-depth research. This study aimed to investigate the specific molecular mechanisms of PTGES and TFAP2C in gefitinib resistance in LUAD. The results indicated that PTGES and TFAP2C were considerably overexpressed in LUAD tissues and cells. Chromatin immunoprecipitation and dual luciferase assay validated that TFAP2C targeted the PTGES promoter region. In addition, gene set enrichment analysis results demonstrated the notable enrichment of PTGES in the NOTCH3 signaling pathway. Overexpression of PTGES remarkably enhanced the viability of PC-9/GR (gefitinib-resistant) cells and their response to gefitinib resistance, which was reversed by the addition of a NOTCH3 inhibitor. Furthermore, overexpressing PTGES upon the TFAP2C silence restored the great inhibition effect conferred by TFAP2C silence in PC-9/GR cells on cell viability and cell response to gefitinib resistance. This study confirmed that TFAP2C can transcriptionally activate PTGES through the NOTCH3 signaling pathway to enhance the response of LUAD cells to gefitinib resistance, proffering a new approach for the treatment of gefitinib resistance in LUAD cells.
Keywords: NOTCH3; PTGES; TFAP2C; gefitinib resistance; lung adenocarcinoma.
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