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Radyoterapinin Metastatik Meme Kanseri Hücrelerindeki Mitokondri İlişkili Yolaklar Üzerine Etkisi

Year 2024, Volume: 7 Issue: 3, 86 - 95, 03.01.2025

Aynur Karadağ Gürel

https://doi.org/10.33713/egetbd.1597405

Abstract

AMAÇ: Radyoterapi, meme kanserinin tedavisinde önemli bir yöntemdir; ancak metastatik ve metastatik olmayan meme kanseri hücrelerinde mitokondri ilişkili yolaklar üzerindeki etkileri tam olarak anlaşılamamıştır. Bu çalışma, radyoterapinin mitokondri fonksiyonu ve ilişkili sinyal yolakları üzerindeki etkilerini, kanser hücrelerinin hayatta kalma, apoptoz ve metastatik ilerlemedeki rollerine odaklanarak incelemektedir.
GEREÇ VE YÖNTEM: MCF-7 ve MDA-MB-231 metastatik meme kanseri hücre serileri kullanılan GEO veri tabanından meme kanseri verilerine ait GSE210306 erişim numarasına sahip ekspresyon verisi kullanılmıştır. Farklı şekilde ifade edilen genleri (DEG) bulmak için GEO2R ile analiz edildi. DEG’ler için GO ve KEGG zenginleştirme analizleri gerçekleştirilmiştir. Cytoscape yazılımıyla bir protein-protein etkileşimi (PPI) ağı oluşturuldu ve radyo terapi sonrası etkilenen mitokondri ilişkili önemli genler belirlendi.
BULGULAR: GEO2R ile analiz sonucunda adjP-değeri <0.05 ve log2FC≥1 veya ≤1 olan DEG'ler seçildi. Örneklerin karşılaştırılması MCF 7 WT vs MDA MB 231 WT ve MCF 7 RR vs MDA MB 231 RR olarak gerçekleştirildi. MCF 7 WT vs MDA MB 231 WT grubunda ifadesi azalan 759 gen 655 ifadesi artan gen bulunmuştur. MCF 7 RR vs MDA MB 231 RR karşılaştırılmasında 693 ifadesi artan 1084 ifadesi azalan gen bulunmuştur. Daha sonra bu genler 1140 mitokondriyle ilişkili gen listesi ile karşılaştırılmış ve ortak gen sayıları şekilde gösterilmiştir
SONUÇ: Bu çalışmanın sonuçları, ortaya çıkan yolak ve genlerin radyoterapi sonrası metastatik hücrelerde etkinliğini ve mitokondri üzerinden değişen yolakların önemli bir rolü olabileceğini göstermiştir. Bu bulgular, mitokondri ilişkili yolakların, meme kanseri hücrelerinin radyoterapiye verdiği yanıtı modüle etmede önemli bir role sahip olduğunu vurgulamaktadır. Bu mekanizmaların anlaşılması, özellikle agresif ve metastatik meme kanseri alt tiplerinde radyoterapinin etkinliğini artırmaya yönelik hedefe yönelik müdahaleler için yeni yollar açabilir.

Keywords

Meme kanseri mitokondri biyoinformatik analiz GEO metastaz

References

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  • Karadağ A, Gürel S (01 Ağustos 2022) Pediatrik Obezite ile İlişkili Anahtar Genlerin ve Yolakların Tanımlanması. Ege Tıp Bilimleri Dergisi 5 2 51–57. Doi: 10.33713/egetbd.1156405
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  • Liu, Z., Fan, M., Hou, J. et al. Serine hydroxymethyltransferase 2 knockdown induces apoptosis in ccRCC by causing lysosomal membrane permeabilization via metabolic reprogramming. Cell Death Dis 14, 144 (2023). Doi:10.1038/s41419-023-05677-4 [CrossRef]
  • Lai SW, Weng PW, Yadav VK, Pikatan NW, Yeh CT, Hsieh MS, Chou CL. Underlying mechanisms of novel cuproptosis-related dihydrolipoamide branched-chain transacylase E2 (DBT) signature in sunitinib-resistant clear-cell renal cell carcinoma. Aging (Albany NY). 2024 Feb 1;16(3):2679-2701. doi: 10.18632/aging.205504. [CrossRef]
  • Xia J, Li S, Liu S, Zhang L. Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets. MedComm (2020). 2023 Jan 16;4(1):e195. Doi: 10.1002/mco2.195. [CrossRef]
  • Karadağ Gürel A, Gürel S. Identification of novel potential molecular targets associated with pediatric septic shock by integrated bioinformatics analysis and validation of in vitro septic shock model: Identifies hub genes associated with pediatric septic shock. J Surg Med . 2022 Dec. 1 ;6(12):932-8.Doi: 10.28982/josam.7461. [CrossRef]
  • Hekmatshoar Y, Karadağ Gürel A. Entegre miRNA/mRNA düzenleyici ağ analizi ile Glioblastomda temozolomid direnç faktörlerinin belirlenmesi. Ege Tıp Bilimleri Dergisi 6 3 73–83. Doi: 10.33713/egetbd.1400022. [CrossRef] Karadağ Gürel Radyoterapinin Mitokondri İlişkili Yolaklar Üzerine Etkisi

Year 2024, Volume: 7 Issue: 3, 86 - 95, 03.01.2025

Aynur Karadağ Gürel

https://doi.org/10.33713/egetbd.1597405

Abstract

References

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. (2021) 71:209–49. doi: 10.3322/caac.21660.
  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. (2011) 144:646–74. doi: 10.1016/j.cell.2011.02.013. [CrossRef]
  • Spencer NY, Stanton RC. The warburg effect, lactate, and nearly a century of trying to cure cancer. Semin Nephrol. (2019) 39:380–93. doi: 10.1016/j.semnephrol.2019.04.007. [CrossRef]
  • Chen F, Chen J, Yang L, Liu J, Zhang X, Zhang Y, et al. Extracellular vesicle-packaged HIF-1α-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells. Nat Cell Biol. (2019) 21(4):498–510. doi: 10.1038/s41556-019-0299-0. [CrossRef]
  • Smolková K, Plecitá-Hlavatá L, Bellance N, Benard G, Rossignol R, Ježek P. Waves of gene regulation suppress and then restore oxidative phosphorylation in cancer cells. Int J Biochem Cell Biol. (2011) 43:950–68. doi: 10.1016/j.biocel.2010.05.003. [CrossRef]
  • Chew EGY, Lim TC, Leong MF, Liu X, Sia YY, Leong ST, et al. Observations that suggest a contribution of altered dermal papilla mitochondrial function to androgenetic alopecia. Exp Dermatol. (2022) 31(6):906–17. doi: 10.1111/exd.14536.
  • Kirtonia A, Sethi G, Garg M. The multifaceted role of reactive oxygen species in tumorigenesis. Cell Mol Life Sci. (2020) 77:4459–83. doi: 10.1007/s00018-020-03536-5. [CrossRef]
  • Lee HY, Nga HT, Tian J, Yi HS. Mitochondrial metabolic signatures in hepatocellular carcinoma. Cells. (2021) 10:1901. doi: 10.3390/cells10081901. [CrossRef]
  • Zhang G, Frederick DT, Wu L, Wei Z, Krepler C, Srinivasan S, et al. Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors. J Clin Invest. (2016) 126(5):1834– 56. doi: 10.1172/JCI82661. [CrossRef]
  • Guo X, Xiang C, Zhang Z, Zhang F, Xi T, Zheng L. Displacement of bax by BMF mediates STARD13 3’UTR-induced breast cancer cells apoptosis in an miRNA-depedent manner. Mol Pharm. (2018) 15:63–71. doi: 10.1021/acs.molpharmaceut. [CrossRef]
  • Greene KS, Lukey MJ, Wang X, Blank B, Druso JE, Lin MJ, et al. SIRT5 stabilizes mitochondrial glutaminase and supports breast cancer tumorigenesis. Proc Natl Acad Sci U S A. (2019) 116(52):26625–32. doi: 10.1073/pnas.1911954116 . [CrossRef]
  • Hekmatshoar, Y., Rahbar Saadat, Y., Ozkan, T., Bozkurt, S., & Karadag Gurel, A. (2023). Identification of common genes and pathways underlying imatinib and nilotinib treatment in CML: a Bioinformatics Study. Nucleosides, Nucleotides & Nucleic Acids, 43(7), 664–684. Doi:10.1080/15257770.2023.2296021. [CrossRef]
  • Karadağ Gürel A, Gürel S. To detect potential pathways and target genes in infantile Pompe patients using computational analysis. Bioimpacts. 2022;12(2):89-105. doi: 10.34172/bi.2022.23467. [CrossRef]
  • Karadağ A, Gürel S (01 Ağustos 2022) Pediatrik Obezite ile İlişkili Anahtar Genlerin ve Yolakların Tanımlanması. Ege Tıp Bilimleri Dergisi 5 2 51–57. Doi: 10.33713/egetbd.1156405
  • Kwon YS, Lee MG, Baek J, Kim NY, Jang H, Kim S. Acyl-CoA synthetase-4 mediates radioresistance of breast cancer cells by regulating FOXM1. Biochem Pharmacol. 2021 Oct;192:114718. DOI: 10.1016/j.bcp.2021.114718. [CrossRef]
  • Jabbari N, Akbariazar E, Feqhhi M, Rahbarghazi R, Rezaie J. Breast cancer-derived exosomes: Tumor progression and therapeutic agents. J Cell Physiol. 2020 Oct;235(10):6345-6356. Doi: 10.1002/jcp.29668. [CrossRef]
  • Kiuru, M., Lehtonen, R., Eerola, H. et al. No germline FH mutations in familial breast cancer patients. Eur J Hum Genet 13, 506–509 (2005).Doi:10.1038/sj.ejhg.5201326 [CrossRef]
  • Kerk SA, Garcia-Bermudez J, Birsoy K, Sherman MH, Shah YM, Lyssiotis CA. Spotlight on GOT2 in Cancer Metabolism. Onco Targets Ther. 2023 Aug 22;16:695-702. Doi: 10.2147/OTT.S382161 [CrossRef]
  • Li, Jj., Yu, T., Zeng, P. et al. Wild-type IDH2 is a therapeutic target for triple-negative breast cancer. Nat Commun 15, 3445 (2024). Doi: 10.1038/s41467-024-47536-6. [CrossRef]
  • Liu, Z., Fan, M., Hou, J. et al. Serine hydroxymethyltransferase 2 knockdown induces apoptosis in ccRCC by causing lysosomal membrane permeabilization via metabolic reprogramming. Cell Death Dis 14, 144 (2023). Doi:10.1038/s41419-023-05677-4 [CrossRef]
  • Lai SW, Weng PW, Yadav VK, Pikatan NW, Yeh CT, Hsieh MS, Chou CL. Underlying mechanisms of novel cuproptosis-related dihydrolipoamide branched-chain transacylase E2 (DBT) signature in sunitinib-resistant clear-cell renal cell carcinoma. Aging (Albany NY). 2024 Feb 1;16(3):2679-2701. doi: 10.18632/aging.205504. [CrossRef]
  • Xia J, Li S, Liu S, Zhang L. Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets. MedComm (2020). 2023 Jan 16;4(1):e195. Doi: 10.1002/mco2.195. [CrossRef]
  • Karadağ Gürel A, Gürel S. Identification of novel potential molecular targets associated with pediatric septic shock by integrated bioinformatics analysis and validation of in vitro septic shock model: Identifies hub genes associated with pediatric septic shock. J Surg Med . 2022 Dec. 1 ;6(12):932-8.Doi: 10.28982/josam.7461. [CrossRef]
  • Hekmatshoar Y, Karadağ Gürel A. Entegre miRNA/mRNA düzenleyici ağ analizi ile Glioblastomda temozolomid direnç faktörlerinin belirlenmesi. Ege Tıp Bilimleri Dergisi 6 3 73–83. Doi: 10.33713/egetbd.1400022. [CrossRef] Karadağ Gürel Radyoterapinin Mitokondri İlişkili Yolaklar Üzerine Etkisi
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Details

Primary Language Turkish
Subjects Signal Transduction, Biochemistry and Cell Biology (Other)
Journal Section Original Investigation
Authors

Aynur Karadağ Gürel 0000-0002-5499-5168

Early Pub Date January 3, 2025
Publication Date January 3, 2025
Submission Date December 6, 2024
Acceptance Date December 30, 2024
Published in Issue Year 2024 Volume: 7 Issue: 3

Cite

EndNote Karadağ Gürel A (January 1, 2025) Radyoterapinin Metastatik Meme Kanseri Hücrelerindeki Mitokondri İlişkili Yolaklar Üzerine Etkisi. Ege Tıp Bilimleri Dergisi 7 3 86–95.
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