Role of MicroRNAs on Anti-Apoptotic MCL-1/cIAP-2 Gene Expression in Patients With EGFR-Mutated NSCLC

The low survival rate in lung cancer is mainly a result of 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 critical role in regulating biological functions, including apoptosis, which is highly relevant to cancer progression. Results of a study that assessed the impact of miR-29a and miR-143 on gene expression were presented at the ESMO Targeted Anticancer Therapies Congress 2024.

The researchers screened patients with NSCLC for mutations and utilized bioinformatics to predict the regulatory potential of miR-29a and miR-143 on MCL-1 and cIAP-2 expression and then examined the expression of MCL-1, cIAP-2, miR-29a, and miR-143 in patients with adenocarcinoma with or without EGFR mutations.

Results showed that patients with mutated EGFR showed higher expression levels of MCL-1 and cIAP-2 genes compared with those with wild-type EGFR. However, patients carrying EGFR mutations showed lower expression levels of miR-29a and miR-143 compared with those with wild-type EGFR. The researchers found overexpression of miR-29a and miR-143 led to significant downregulation of MCL-1 and cIAP-2 expression in cell culture experiments. Dual-luciferase reporter experiments confirmed that miR-29a targets MCL-1 mRNA and
miR-143 targets cIAP-2 mRNA.

The researchers concluded that “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.”

Source: Abrehdari-Tafreshi Z. 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. Abstract 57P. Presented at the ESMO Targeted Anticancer Therapies Congress 2024; February 26-28, 2024; Paris, France.