Research Article

DOI :10.26650/JARHS2025-1642012 IUP :10.26650/JARHS2025-1642012 Full Text (PDF)

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

Vahideh Zarerajabi, Burcu Salman Yaylaz, Sema Sırma Ekmekçi, Neslihan Abacı

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.

Keywords: DHRS2, BRCA1, non-small cell lung cancer, DNA damage response

DOI :10.26650/JARHS2025-1642012 IUP :10.26650/JARHS2025-1642012 Full Text (PDF)

DHRS2'nin Küçük Hücre Dişi Akciğer Kanserinde BRCA1 Ekspresyonunun Düzenlenmesindeki Rolü

Vahideh Zarerajabi, Burcu Salman Yaylaz, Sema Sırma Ekmekçi, Neslihan Abacı

Amaç: Küçük hücre dışı akciğer kanseri (KHDAK), kansere bağlı ölümlerin önde gelen nedenlerinden biridir ve genellikle ileri evrede teşhis edilir. DHRS2, lipid metabolizması, hormon regülasyonu ve oksidatif stresle ilişkili olup, p53 stabiliza syonu ve MDM2 inhibisyonu yoluyla kanser progresyonunu etkileyen önemli bir tümör baskılayıcıdır. TP53 ve BRCA1, DNA hasar yanıtı ve tümör baskılama süreç lerinde kritik roller oynarken, BRCA1 aynı zamanda KHDAK’de prognostik bir belirteç olarak öne çıkmaktadır. Bu çalışma, KHDAK hücrelerinde DHRS2 ekspresyon düzey leri ile BRCA1 arasındaki etkileşimleri inceleyerek, moleküler mekanizmalarını daha iyi anlamayı ve yeni terapötik hedefler ile tedavi stratejileri geliştirmeyi amaçla maktadır.

Gereç ve Yöntemler: Bu çalışmada ekspresyon vektörü kullanılarak akciğer kanser hücre hatları (A549, H1299) ve normal bronş epitel hücre hattında (BEAS-2B), DHRS2 aşırı ekspresyonu sağlanmış ve quantitative PCR (qPCR) ile doğrulanmıştır. Ardından, DHRS2 aşırı ekspresyonunun BRCA1 ekspresyon seviyeleri üzerindeki etkisi incelenmiştir. Ayrıca KHDAK'nin alt tiplerinde BRCA1 ekspresyon düzeyleri GEPIA2, BRCA1 ve DHRS2 genlerindeki genomik değişiklikler ise cBioPortal-TCGA ile incelenmiştir.

Bulgular: DHRS2’nin aşırı ekspresyonu, A549 hücrelerinde (p53 wild type) BRCA1 ekspresyonunu azaltırken, H1299 hücrelerinde (p53 null) herhangi bir değişikliğe neden olmamaktadır. BEAS-2B hücre hattında ise DHRS2’nin aşırı ekspresyonu BRCA1 ekspresyonunu baskılamaktadır. GEPIA2 verileri, BRCA1'in tümör dokularında normal dokulara kıyasla belirgin şekilde arttığını göstermektedir. Genomik değişik lik analizi, BRCA1'deki amplifikasyonlar ve delesyonlar, genomik instabiliteyi işaret ederken, DHRS2'nin daha az mutasyon sergilemesi, düzenleyici rolünü ortaya koy maktadır.

Sonuç: Elde ettiğimiz bulgular DHRS2'nin BRCA1 ekspresyonunu modüle edebile ceğini ve p53’ün bu süreçte kritik rol oynayabileceğini göstermektedir. BRCA1 ve DHRS2'deki genetik değişiklikler, KHDAK tümörigenezinde etkili olduğunu düşündürmektedir, gelecekteki çalışmalarla DHRS2 ve p53 aracılı mekanizmaları daha ayrıntılı incelemelidir.

Keywords: DHRS2, BRCA1, Küçük hücreli dışı akciğer kanseri, DNA hasar yanıtı

References

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020;70(1):7-30. google scholar
Liang Z, Zhong Y, Meng L, Chen Y, Liu Y, Wu A, et al. HAX1 enhances the survival and metastasis of non-small cell lung cancer through the AKT/mTOR and MDM2/p53 signaling pathway. Thorac Cancer 2020;11(11):3155-67. google scholar
Gabrielli F, Tofanelli S. Molecular and functional evolution of human DHRS2 and DHRS4 duplicated genes. Gene 2012;511(2):461-9. google scholar
Pellegrini S, Censini S, Guidotti S, Iacopetti P, Rocchi M, Bianchi M, et al. A human short-chain dehydrogenase/reductase gene: structure, chromosomal localization, tissue expression and subcellular localization of its product. Biochim Biophys Acta 2002;1574(3):215-22. google scholar
Li Z, Liu H, Bode A, Luo X. Emerging roles of dehydrogenase/reductase member 2 (DHRS2) in the pathology of disease. Eur J Pharmacol 2021;898:173972. google scholar
Steffens Reinhardt L, Groen K, Newton C, Avery-Kiejda KA. The role of truncated p53 isoforms in the DNA damage response. Biochim Biophys Acta Rev Cancer 2023;1878(3):188882. google scholar
Rosen EM, Fan S, Isaacs C. BRCA1 in hormonal carcinogenesis: basic and clinical research. Endocr Relat Cancer 2005;12(3):533-48. google scholar
Gachechiladze M, Skarda J. The role of BRCA1 in non-small cell lung cancer. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2012;156(3):200-3. google scholar
Zhou Y, Wang L, Ban X, Zeng T, Zhu Y, Li M, et al. DHRS2 inhibits cell growth and motility in esophageal squamous cell carcinoma. Oncogene 2018;37(8):1086-94. google scholar
Yamada H, Arakawa Y, Saito S, Agawa M, Kano Y, Horiguchi-Yamada J. Depsipeptide-resistant KU812 cells show reversible P-glycoprotein expression, hyper-acetylated histones, and modulated gene expression profile. Leuk Res 2006;30(6):723-34. google scholar
An Z, Bo W, Qin J, Jiang L, Jiang J. Auxiliary Diagnosis and Prognostic Value of Dehydrogenase/Reductase 2 (DHRS2) in Various Tumors. Iran J Public Health 2023;52(6):1150-60. google scholar
Han Y, Song C, Wang J, Tang H, Peng Z, Lu S. HOXA13 contributes to gastric carcinogenesis through DHRS2 interacting with MDM2 and confers 5-FU resistance by a p53-dependent pathway. Mol Carcinog 2018;57(6):722-34. google scholar
Jiang J, Yang ES, Jiang G, Nowsheen S, Wang H, Wang T, et al. p53-dependent BRCA1 nuclear export controls cellular susceptibility to DNA damage. Cancer Res 2011;71(16):5546-57. google scholar

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APA

Zarerajabi, V., Salman Yaylaz, B., Ekmekçi, S.S., & Abacı, N. (2019). The Role of DHRS2 in the Regulation of BRCA1 Expression in Non-small Cell Lung Cancer. Journal of Advanced Research in Health Sciences, 0(0), -. https://doi.org/10.26650/JARHS2025-1642012

AMA

Zarerajabi V, Salman Yaylaz B, Ekmekçi S S, Abacı N. The Role of DHRS2 in the Regulation of BRCA1 Expression in Non-small Cell Lung Cancer. Journal of Advanced Research in Health Sciences. 2019;0(0):-. https://doi.org/10.26650/JARHS2025-1642012

ABNT

Zarerajabi, V.; Salman Yaylaz, B.; Ekmekçi, S.S.; Abacı, N. The Role of DHRS2 in the Regulation of BRCA1 Expression in Non-small Cell Lung Cancer. Journal of Advanced Research in Health Sciences, [Publisher Location], v. 0, n. 0, p. -, 2019.

Chicago: Author-Date Style

Zarerajabi, Vahideh, and Burcu Salman Yaylaz and Sema Sırma Ekmekçi and Neslihan Abacı. 2019. “The Role of DHRS2 in the Regulation of BRCA1 Expression in Non-small Cell Lung Cancer.” Journal of Advanced Research in Health Sciences 0, no. 0: -. https://doi.org/10.26650/JARHS2025-1642012

Chicago: Humanities Style

Zarerajabi, Vahideh, and Burcu Salman Yaylaz and Sema Sırma Ekmekçi and Neslihan Abacı. “The Role of DHRS2 in the Regulation of BRCA1 Expression in Non-small Cell Lung Cancer.” Journal of Advanced Research in Health Sciences 0, no. 0 (Jun. 2025): -. https://doi.org/10.26650/JARHS2025-1642012

Harvard: Australian Style

Zarerajabi, V & Salman Yaylaz, B & Ekmekçi, SS & Abacı, N 2019, 'The Role of DHRS2 in the Regulation of BRCA1 Expression in Non-small Cell Lung Cancer', Journal of Advanced Research in Health Sciences, vol. 0, no. 0, pp. -, viewed 26 Jun. 2025, https://doi.org/10.26650/JARHS2025-1642012

Harvard: Author-Date Style

Zarerajabi, V. and Salman Yaylaz, B. and Ekmekçi, S.S. and Abacı, N. (2019) ‘The Role of DHRS2 in the Regulation of BRCA1 Expression in Non-small Cell Lung Cancer’, Journal of Advanced Research in Health Sciences, 0(0), pp. -. https://doi.org/10.26650/JARHS2025-1642012 (26 Jun. 2025).

MLA

Zarerajabi, Vahideh, and Burcu Salman Yaylaz and Sema Sırma Ekmekçi and Neslihan Abacı. “The Role of DHRS2 in the Regulation of BRCA1 Expression in Non-small Cell Lung Cancer.” Journal of Advanced Research in Health Sciences, vol. 0, no. 0, 2019, pp. -. [Database Container], https://doi.org/10.26650/JARHS2025-1642012

Vancouver

Zarerajabi V, Salman Yaylaz B, Ekmekçi SS, Abacı N. The Role of DHRS2 in the Regulation of BRCA1 Expression in Non-small Cell Lung Cancer. Journal of Advanced Research in Health Sciences [Internet]. 26 Jun. 2025 [cited 26 Jun. 2025];0(0):-. Available from: https://doi.org/10.26650/JARHS2025-1642012 doi: 10.26650/JARHS2025-1642012

ISNAD

Zarerajabi, Vahideh - Salman Yaylaz, Burcu - Ekmekçi, SemaSırma - Abacı, Neslihan. “The Role of DHRS2 in the Regulation of BRCA1 Expression in Non-small Cell Lung Cancer”. Journal of Advanced Research in Health Sciences 0/0 (Jun. 2025): -. https://doi.org/10.26650/JARHS2025-1642012

TIMELINE

Submitted	18.02.2025
Accepted	26.03.2025
Published Online	28.05.2025

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Journal of Advanced Research in Health Sciences