The Role of DHRS2 in the Regulation of BRCA1 Expression in Non-small Cell Lung Cancer

<strong>Objective:</strong> Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality and is often diagnosed late. <em>DHRS2 </em>regulates lipid metabolism, hormones, and oxidative stress, acting as a tumour suppressor by stabilising p53 and inhibiting MDM2. Tp53 and <em>BRCA1 </em>are crucial for DNA repair and tumour suppression, with <em>BRCA1 </em>as a prognostic marker in NSCLC. However, the interaction between <em>DHRS2 </em>and <em>BRCA1 </em>in NSCLC remains unclear. This study aimed to examine how <em>DHRS2 </em>expression influences <em>BRCA1 </em>levels in NSCLC cells, providing insight into potential therapeutic targets. <strong>Material and Methods:</strong> <em>DHRS2 </em>overexpression was induced in NSCLC cells (A549, H1299) and normal bronchial epithelial cells (BEAS-2B) using an expression vector and confirmed by quantitative PCR (qPCR). The effect of <em>DHRS2 </em>overexpression on <em>BRCA1 </em>expression levels was examined. In addition, <em>BRCA1 </em>expression levels in NSCLC subtypes were analysed using GEPIA2, while genomic alterations in <em>BRCA1 </em>and <em>DHRS2 </em>were investigated via cBioPortal-TCGA. <strong>Results: </strong><em>DHRS2 </em>overexpression led to a decrease in <em>BRCA1 </em>expression in A549 cells (p53 wild-type) but had no effect in H1299 cells (p53-null). In BEAS-2B cells, <em>DHRS2 </em>overexpression also resulted in <em>BRCA1 </em>suppression. GEPIA2 analysis showed significantly higher <em>BRCA1</em> expression in tumour tissues. Genomic analysis revealed frequent <em>BRCA1 </em>alterations, indicating instability, whereas <em>DHRS2 </em>had fewer muta tions, implying a regulatory role. <strong>Conclusion: </strong>This study demonstrates that <em>DHRS2 </em>modulates <em>BRCA1 </em>expression through a p53-dependent mechanism. Genetic alterations in <em>BRCA1 </em>and <em>DHRS2 </em>indicate their potential involvement in NSCLC tumorigenesis. Future studies should further investigate the mechanisms mediated by <em>DHRS2 </em>and p53 to elucidate their roles in cancer progression.