57P The role of mir29-a and mir143 on the anti-apoptotic MCL-1/cIAP-2 genes expression in EGFR mutated non-small cell lung carcinoma patients

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Lung cancer has a low survival rate, largely due to drug resistance in patients with key gene mutations. Tumor drug resistance often involves overexpression of anti-apoptotic genes, which are influenced by EGFR signaling. Additionally, microRNAs (miRNAs) play a crucial role in regulating biological functions such as apoptosis, which is highly relevant to cancer progression. To conduct this study, we screened non-small cell lung carcinoma patients for mutations and utilized bioinformatics to predict the regulatory potential of miRNAs (miR-29a, miR-143) on MCL-1 and cIAP-2 expression. We then examined the expression of MCL-1, cIAP-2, miR-29a, and miR-143 in adenocarcinoma patients with or without EGFR mutations. To assess the impact of miR-29a and miR-143 on gene expression, we conducted overexpression and luciferase assays using HEK-293T cells. Patients with mutated EGFR showed higher expression levels of MCL-1 and cIAP-2 genes compared to those with wild-type EGFR. Conversely, patients carrying EGFR mutations exhibited lower expression levels of miR-29a and miR-143 compared to those with wild-type EGFR. In cell culture experiments, overexpression of miR-29a and miR-143 led to significant downregulation of MCL-1 and cIAP-2 expression. Dual-luciferase reporter experiments confirmed that miR-29a targets MCL-1 mRNA and miR-143 targets cIAP-2 mRNA. Our findings indicate that increased EGFR signaling in lung cancer cells may elevate the expression of anti-apoptotic MCL-1 and cIAP-2 genes, potentially through the downregulation of miR-29a-3p and miR-143-3p.

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