Hastalıkların Tedavisinde Umut Vadeden Yeni Hedef: FOXO Transkripsiyon Faktörleri

Year 2022, Volume: 2 Issue: 1, 25 - 32, 03.04.2022

Nihal Vuranok

https://doi.org/10.29228/HMJ.11

Abstract

Hücreler, hayatta kalmak veya apoptozun hücresel cevabını koordine edebilmek için ayrıntılı mekanizmalar geliştirmiştir. Forkhead box-O transkripsiyon faktörleri (FOXO); DNA hasar onarımı, hücre döngüsü ilerlemesi ve durdurulması, oksidatif stres tepkisi ve redoks sinyali, glukoneogenez ve apoptoz ile ilgili genlerin ekspresyonunu düzenleyerek çeşitli hücresel süreçlerin yürütülmesinde kritik rol oynamaktadır. FOXO transkripsiyon faktörlerinin fonksiyonu; fosforilasyon, asetilasyon ve ubiküitinasyon gibi translasyon sonrası modifikasyonlar ve nükleer sitoplazmik geçiş ile sıkı bir şekilde kontrol edilmektedir. Yapılan çalışmalar; FOXO aktivitesinin düzenleyici etkisinin, oksidatif stres dahil olmak üzere farklı uyaranlara yanıt olarak oluştuğunu göstermektedir. FOXO transkripsiyon faktörlerinin transkripsiyon sonrası modifikasyonundaki anormallikler sıklıkla çeşitli hastalık durumlarıyla bağlantılıdır. Bu çalışmada, bilim insanlarına yeni araştırma fikirleri sunmak amacıyla FOXO transkripsiyon faktörleri’ nin tanımı ve sınıflandırılması, oksidatif stres ve kanser dahil olmak üzere çeşitli fizyolojik ve patofizyolojik koşullar altında transkripsiyon sonrası FOXO modifikasyonları ve FOXO' ların tümör baskılayıcı özelliklerinin terapötik olarak klinik kullanımı literatür bilgisi ışığında araştırılarak derlendi.

Keywords

FOXO, HASTALIK, İLAÇ, TRANSKRİPSİYON FAKTÖRLERİ

Promising New Target in the Treatment of Diseases: FOXO Transcription Factors

Abstract

Cells have evolved elaborate mechanisms to survive or coordinate the cellular response to apoptosis. Forkhead box-O transcription factors (FOXOs); It plays critical roles in the execution of various cellular processes by regulating the expression of genes involved in DNA damage repair, cell cycle progression and arrest, oxidative stress response and redox signaling, gluconeogenesis and apoptosis. Function of FOXO transcription factors; It is tightly controlled by post-translational modifications such as phosphorylation, acetylation and ubiquitination, and nuclear cytoplasmic transition. Made works; It shows that the regulatory effect of FOXO activity occurs in response to different stimuli, including oxidative stress. Abnormalities in post-transcriptional modification of FOXO transcription factors are frequently associated with various disease states. In this study; In order to present new research ideas to scientists, the definition and classification of FOXO transcription factors, post-transcriptional FOXO modifications under various physiological and pathophysiological conditions, including oxidative stress and cancer, and the clinical use of FOXO's tumor suppressor properties as therapeutics were investigated and compiled in the light of literature.

Keywords

DISEASE, FOXO, MEDICINE, TRANSCRIPTION FACTORS

References

• 1. Referans1. Kaestner KH, Knochel W, & Martinez DE. Unified nomenclature for the winged helix/forkhead transcription factors. Genes & development, 2000; 14(2), 142–146.
• 2. Referans2. Lee S, Dong HH. FoxO integration of insulin signaling with glucose and lipid metabolism. The Journal of endocrinology, 2017; 233(2), R67–R79.
• 3. Referans3. Brown AK, Webb AE. Regulation of FOXO Factors in Mammalian Cells. Current topics in developmental biology, 2018; 127, 165–192.
• 4. Referans4. Lu H, & Huang, H. FOXO1: a potential target for human diseases. Current drug targets, 2011; 12(9), 1235–1244.
• 5. Referans5. Webb AE, Pollina EA, Vierbuchen T, Urbán N, et al. FOXO3 shares common targets with ASCL1 genome-wide and inhibits ASCL1-dependent neurogenesis. Cell reports, 2013; 4(3), 477–491.
• 6. Referans6. Huang H, Tindall J. Dynamic FoxO transcription factors. J Cell Sci, 2007; 120 (15): 2479–2487.
• 7. Referans7. Wang Z, Yu T, Huang P. Post-translational modifications of FOXO family proteins (Review). Molecular medicine reports, 2016; 14(6), 4931–4941.
• 8. Referans8. Wang F, Chan CH, Chen K, Guan X, et al. Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation. Oncogene, 2012; 31(12), 1546–1557.
• 9. Referans9. Zhang J, Zhong Q. Histone deacetylase inhibitors and cell death. Cell Mol Life Sci. 2014; 71(20): 3885–3901.
• 10. Referans10. Klotz LO, Sánchez-Ramos C, Prieto-Arroyo L; Urbánek P, et al. Redox regulation of FoxO transcription factors. Redox Biology, 2015; 6, 51–72. doi:10.1016/j.redox.2015.06.019.
• 11. Referans11. Shen M, Cao Y, Jiang Y, Wei Y, et al. Melatonin protects mouse granulosa cells against oxidative damage by inhibiting FOXO1-mediated autophagy: Implication of an antioxidation-independent mechanism. Redox biology,2018; 18, 138–157.
• 12. Referans12. O'Neill BT, Bhardwaj G, Penniman CM, Krumpoch MT, et al. FoxO Transcription Factors Are Critical Regulators of Diabetes-Related Muscle Atrophy. Diabetes, 2019; 68(3), 556–570.
• 13. Referans13. Peng SL. Foxo in the immune system. Oncogene, 2008; 27(16), 2337–2344.
• 14. Referans14. Brunet A, Sweeney LB, Sturgill JF, Chua KF, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science (New York, N.Y.), 2004; 303(5666), 2011–2015.
• 15. Referans15. Lu M, Wan M, Leavens KF, Chu Q, et al. Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1. Nature medicine, 2012; 18(3), 388–395.
• 16. Referans16. Wang D, Wang T, Wang R, Zhang X, et al. Suppression of p66Shc prevents hyperandrogenism-induced ovarian oxidative stress and fibrosis. Journal of translational medicine, 2020; 18(1), 84.
• 17. Referans17. Jang H, Lee OH, Lee Y, Yoon H, et al. Melatonin prevents cisplatin-induced primordial follicle loss via suppression of PTEN/AKT/FOXO3a pathway activation in the mouse ovary. Journal of pineal research, 2016; 60(3), 336–347.
• 18. Referans18. Yang JL, Zhang CP, Li L, Huang L, et al. Testosterone induces redistribution of forkhead box-3a and down-regulation of growth and differentiation factor 9 messenger ribonucleic acid expression at early stage of mouse folliculogenesis. Endocrinology, 2010; 151(2), 774–782.
• 19. Referans19. Liu H, Luo LL, Qian YS, Fu YC, et al. FOXO3a is involved in the apoptosis of naked oocytes and oocytes of primordial follicles from neonatal rat ovaries. Biochemical and biophysical research communications, 2009; 381(4), 722–727.
• 20. Referans20. Matsuda, F, Inoue N, Maeda A, Cheng Y, et al. Expression and function of apoptosis initiator FOXO3 in granulosa cells during follicular atresia in pig ovaries. The Journal of reproduction and development, 2011; 57(1), 151–158.
• 21. Referans21. Yang WB, Chen PH, Hsu T, Fu TF, et al. Sp1-mediated microRNA-182 expression regulates lung cancer progression. Oncotarget, 2014; 5(3), 740–753. https://doi.org/10.18632/oncotarget.1608
• 22. Referans22. Segura MF, Hanniford D, Menendez S, Reavie L, et al. Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proceedings of the National Academy of Sciences of the United States of America, 2009; 106(6), 1814–1819.
• 23. Referans23. Gheysarzadeh A, & Yazdanparast R. STAT5 reactivation by catechin modulates H2O 2-induced apoptosis through miR-182/FOXO1 pathway in SK-N-MC cells. Cell biochemistry and biophysics, 2015; 71(2), 649–656.
• 24. Referans24. Wong HK, Veremeyko T, Patel N, Lemere CA, et al. De-repression of FOXO3a death axis by microRNA-132 and -212 causes neuronal apoptosis in Alzheimer's disease. Human molecular genetics, 2013; 22(15), 3077–3092.
• 25. Referans25. Ucar A, Gupta SK, Fiedler J, Erikci E, et al. The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy. Nature communications, 2012; 3, 1078.
• 26. Referans26. Tang H, Bian Y, Tu C, Wang Z, et al. The miR-183/96/182 cluster regulates oxidative apoptosis and sensitizes cells to chemotherapy in gliomas. Current cancer drug targets, 2013; 13(2), 221–231.
• 27. Referans27. Lennicke C, Rahn J, Lichtenfels R, Wessjohann LA, et al. Hydrogen peroxide - production, fate and role in redox signaling of tumor cells. Cell communication and signaling: CCS, 2015; 13, 39.
• 28. Referans28. Fu Z, Tindall DJ. FOXOs, cancer and regulation of apoptosis. Oncogene, 2008; 27(16), 2312–2319.
• 29. Referans29. Trinh DL, Scott DW, Morin RD, Mendez-Lago M, et al. Analysis of FOXO1 mutations in diffuse large B-cell lymphoma. Blood, 2013; 121(18), 3666–3674.
• 30. Referans30. Fitzwalter BE, Towers CG, Sullivan KD, Andrysik Z, et al. Autophagy Inhibition Mediates Apoptosis Sensitization in Cancer Therapy by Relieving FOXO3a Turnover. Developmental cell, 2018; 44(5), 555–565.e3.
• 31. Referans31. Yan H, Wu A. FOXO1 is crucial in glioblastoma cell tumorigenesis and regulates the expression of SIRT1 to suppress senescence in the brain. Molecular medicine reports, 2018; 17(2), 2535–2542.
• 32. Referans32. Zhu WL, Tong H, Teh JT, Wang M. Forkhead box protein O3 transcription factor negatively regulates autophagy in human cancer cells by inhibiting forkhead box protein O1 expression and cytosolic accumulation. PloS one, 2014; 9(12), e115087.
• 33. Referans33. O'Neill F, Madden SF, Clynes M, Crown J, et al. A gene expression profile indicative of early stage HER2 targeted therapy response. Molecular cancer, 2013; 12, 69.
• 34. Referans34. Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science (New York, N.Y.), 2007; 318(5858), 1931–1934.
• 35. Referans35. Mutka SC, Yang WQ, Dong SD, Ward SL, et al. Identification of nuclear export inhibitors with potent anticancer activity in vivo. Cancer research, 2009; 69(2), 510–517.
• 36. Referans36. Link W, Oyarzabal J, Serelde BG, Albarran MI, et al. Chemical interrogation of FOXO3a nuclear translocation identifies potent and selective inhibitors of phosphoinositide 3-kinases. The Journal of biological chemistry, 2009; 284(41), 28392–28400.
• 37. Referans37. Wang B, Yang Q, Sun YY, Xing YF, et al. Resveratrol-enhanced autophagic flux ameliorates myocardial oxidative stress injury in diabetic mice. Journal of cellular and molecular medicine, 2014; 18(8), 1599–1611.
• 38. Referans38. Hornsveld M, Smits L, Meerlo M, van Amersfoort M, et al. FOXO Transcription Factors Both Suppress and Support Breast Cancer Progression. Cancer research, 2018; 78(9), 2356–2369.
• 39. Referans39. Liu L, Tao Z, Zheng LD, Brooke JP, et al. FoxO1 interacts with transcription factor EB and differentially regulates mitochondrial uncoupling proteins via autophagy in adipocytes. Cell death discovery, 2016; 2, 16066.