Elevated SRC3 expression predicts pemetrexed resistance in lung adenocarcinoma

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Lung cancer is a leading cause of cancer death globally.
• Pemetrexed is a key chemotherapy for lung adenocarcinoma, but resistance is common.
• Mechanisms of pemetrexed resistance are not well understood.

Purpose of the Study:

• To investigate the molecular mechanisms of pemetrexed resistance in lung adenocarcinoma.
• To identify potential therapeutic targets and biomarkers for pemetrexed resistance.

Main Methods:

• RNA sequencing (RNA-seq) to compare gene expression in sensitive and resistant cells.
• Functional assays to assess the role of SRC3 in chemoresistance.
• Analysis of signaling pathways (Nrf2, AKT) and apoptosis.

Main Results:

• SRC3 was significantly upregulated in pemetrexed-resistant lung adenocarcinoma cells.
• SRC3 overexpression conferred resistance to pemetrexed by reducing apoptosis and reactive oxygen species (ROS) levels.
• SRC3 regulates pemetrexed resistance through the Nrf2 and AKT signaling pathways.
• High SRC3 expression correlated with poor response to pemetrexed and worse clinical outcomes.

Conclusions:

• SRC3 plays a critical role in promoting pemetrexed resistance in lung adenocarcinoma.
• Knockdown of SRC3 could be a strategy to treat pemetrexed-resistant lung cancer.
• SRC3 may serve as a predictive biomarker for pemetrexed responsiveness in lung cancer patients.