@article{article_1642012, title={The Role of DHRS2 in the Regulation of BRCA1 Expression in Non-small Cell Lung Cancer}, journal={Journal of Advanced Research in Health Sciences}, volume={8}, pages={84–90}, year={2025}, DOI={10.26650/JARHS2025-1642012}, author={Zarerajabi, Vahideh and Salman Yaylaz, Burcu and Sırma Ekmekci, Sema and Abacı, Neslihan}, keywords={DHRS2, BRCA1, non-small cell lung cancer, DNA damage response}, abstract={Objective: Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality and is often diagnosed late. DHRS2 regulates lipid metabolism, hormones, and oxidative stress, acting as a tumour suppressor by stabilising p53 and inhibiting MDM2. Tp53 and BRCA1 are crucial for DNA repair and tumour suppression, with BRCA1 as a prognostic marker in NSCLC. However, the interaction between DHRS2 and BRCA1 in NSCLC remains unclear. This study aimed to examine how DHRS2 expression influences BRCA1 levels in NSCLC cells, providing insight into potential therapeutic targets. Material and Methods: DHRS2 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 DHRS2 overexpression on BRCA1 expression levels was examined. In addition, BRCA1 expression levels in NSCLC subtypes were analysed using GEPIA2, while genomic alterations in BRCA1 and DHRS2 were investigated via cBioPortal-TCGA. Results: DHRS2 overexpression led to a decrease in BRCA1 expression in A549 cells (p53 wild-type) but had no effect in H1299 cells (p53-null). In BEAS-2B cells, DHRS2 overexpression also resulted in BRCA1 suppression. GEPIA2 analysis showed significantly higher BRCA1 expression in tumour tissues. Genomic analysis revealed frequent BRCA1 alterations, indicating instability, whereas DHRS2 had fewer muta tions, implying a regulatory role. Conclusion: This study demonstrates that DHRS2 modulates BRCA1 expression through a p53-dependent mechanism. Genetic alterations in BRCA1 and DHRS2 indicate their potential involvement in NSCLC tumorigenesis. Future studies should further investigate the mechanisms mediated by DHRS2 and p53 to elucidate their roles in cancer progression.}, number={2}, publisher={Istanbul University}, organization={Bu çalışma, İstanbul Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından desteklenmiştir.}