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UVEAL MALIGN MELANOMA HASTALARININ SERUM/ PLAZMASINDA YÜKSEK miR-454 EKSPRESYONU

Yıl 2022, Cilt: 5 Sayı: 1, 14 - 19, 10.02.2022
https://doi.org/10.26650/JARHS2022-981726

Öz

Amaç: Uveal malign melanoma (UMM) kötü prognoza sahip, yüksek metastaz eğilimi gösteren ve erken teşhisi zor bir kanser türüdür. Bu nedenle bu hastalıkta non-invaziv diyagnostik ve prognostik biyobelirteçlere ihtiyaç duyulmaktadır. Çalışmamızda UMM tanısı almış hastalar ile sağlıklı kontrollerin periferik kan örneklerindeki miR-454 düzeyi ve ilgili molekülün diyagnostik ve prognostik bir biyobelirteç olma özelliği taşıyıp taşımadığı araştırılmıştır. Gereç ve Yöntem: Bu çalışma İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Göz Hastalıkları Anabilim Dalı ile Onkoloji Enstitüsü’ne başvuran, 72 UMM’li hasta ve bu hasta grubu ile yaş, cinsiyet ve etnik köken açısından eşleştirilmiş 72 sağlıklı kontrolden oluşan bir katılımcı grubunun periferik kan örnekleri kullanılarak gerçekleştirilmiştir. Periferik kan örneklerine ait serum/plazmalardan cell free RNA (cfRNA) izolasyonu yapılarak miR-454 ifade düzeyi gerçek zamanlı Polimeraz Zincir Reaksiyonu (GZ-PZR) ile analiz edilmiştir. Referenas gene göre belirlenen miR-454 ekspresyon düzeyi hasta ve sağlıklı kontroller ile karşılaştırılarak değerlendirilmiştir. Bulgular: Uveal malign melanoma ve sağlıklı kontrol grupları arasında yapılan incelemede, miR-454 ifade düzeyinin sağlıklı kontrollere göre hasta grubunda 4,14 kat arttığı ve istatistiksel olarak anlamlı olduğu saptanmıştır. Çalışmada miR-454 ifade düzeyi ile sigara ve alkol kullanımı arasında anlamlı bir ilişki olduğu gösterilmiştir. Daha sonra miR-454’ün hedef mRNA’ları biyoinformatik araçlarla incelenmiş ve miR-454’ün kanserde tümör baskılayıcı ve onkogenik fonksiyonlara sahip olduğu anlaşılmıştır. Sonuç: Çalışmamız, daha önce çeşitli hücre hatlarında ve UMM tümör dokusunda yüksek ifade düzeyine sahip olduğu bildirilen miR-454’ün UMM hastalarının serum/plazmasında da yüksek düzeyde ifade edildiğini göstermiştir. Periferik kan dolaşımında, özellikle serum/plazmada araştırılan miR-454 ifade düzeyinin UMM’de diyagnostik ve prognostik biyobelirteç olarak kullanılabileceğini ve önemli bir terapötik hedef olarak değerlendirilebileceğini düşündürmektedir.

Destekleyen Kurum

Bu çalışma, İstanbul Üniversitesi Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiştir.

Proje Numarası

Proje No: TDK-2019-35336

Kaynakça

  • 1. Krantz BA et al. Uveal melanoma: epidemiology, etiology, and treatment of primary disease. Clin Ophthalmol 2017;11:279-89.
  • 2. Shields CL et al. American Joint Committee on Cancer classification of posterior uveal melanoma (tumor size category) predicts prognosis in 7731 patients. Ophthalmology 2013;120(10):2066-71.
  • 3. Shields JA, Shields CL. Management of posterior uveal melanoma: past, present, and future: the 2014 Charles L. Schepens lecture. Ophthalmology 2015;122(2):414-28.
  • 4. Eskelin S et al. Tumor doubling times in metastatic malignant melanoma of the uvea: tumor progression before and after treatment. Ophthalmology 2000;107(8):1443-9.
  • 5. Materin MA, Faries M, Kluger HM. Molecular alternations in uveal melanoma. Curr Probl Cancer 2011;35(4):211-24.
  • 6. Dithmar S, Diaz CE, Grossniklaus HE. Intraocular melanoma spread to regional lymph nodes: report of two cases. Retina 2000;20(1):76-9.
  • 7. Koc I, Kiratli H. Current Management of Conjunctival Melanoma Part 2: Treatment and Future Directions. Turk J Ophthalmol 2020;50(6):362-70.
  • 8. Wong JR et al. Management of conjunctival malignant melanoma: a review and update. Expert Rev Ophthalmol 2014;9(3):185-204.
  • 9. Seregard S. Conjunctival melanoma. Surv Ophthalmol 1998;42(4):321-50.
  • 10. Brownstein S. Malignant melanoma of the conjunctiva. Cancer Control 2004;11(5):310-6.
  • 11. Kujala E, Makitie T, Kivela T. Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci 2003;44(11):4651-9.
  • 12. Sun L et al. MicroRNA-454 functions as an oncogene by regulating PTEN in uveal melanoma. FEBS Lett 2015;589(19 Pt B):2791-6.
  • 13. McLaughlin CC et al. Incidence of noncutaneous melanomas in the U.S. Cancer 2005;103(5):1000-7.
  • 14. Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1998;83(8):1664-78.
  • 15. Johansson CC et al. Expression and prognostic significance of iNOS in uveal melanoma. Int J Cancer 2010;126(11):2682-9.
  • 16. Yan D et al. MicroRNA-34a inhibits uveal melanoma cell proliferation and migration through downregulation of c-Met. Invest Ophthalmol Vis Sci 2009;50(4):1559-65.
  • 17. Chen X et al. Epigenetics, microRNAs, and carcinogenesis: functional role of microRNA-137 in uveal melanoma. Invest Ophthalmol Vis Sci 2011;52(3):1193-9.
  • 18. Singh AD, Shields CL, Shields JA. Prognostic factors in uveal melanoma. Melanoma Res 2001;11(3):255-63.
  • 19. Chen X et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008;18(10):997-1006.
  • 20. Gilad S et al. Serum microRNAs are promising novel biomarkers. PLoS One 2008;3(9):e3148.
  • 21. Mitchell PS et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008;105(30):10513-8.
  • 22. Bignotti E et al. Identification of stably expressed reference small non-coding RNAs for microRNA quantification in high-grade serous ovarian carcinoma tissues. J Cell Mol Med 2016;20(12):2341-8.
  • 23. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116(2):281-97.
  • 24. Yi Fan Li, Li Dong, Yang Li, and Wen Bin Wei. A Review of MicroRNA in Uveal Melanoma. Onco Targets Ther 2020;13:6351–9.
  • 25. Zhang L et al. The miR-181 family promotes cell cycle by targeting CTDSPL, a phosphatase-like tumor suppressor in uveal melanoma. J Exp Clin Cancer Res 2018;37(1):15.
  • 26. Peng J, Liu H, Liu C. MiR-155 Promotes Uveal Melanoma Cell Proliferation and Invasion by Regulating NDFIP1 Expression. Technol Cancer Res Treat 2017;16(6):1160-7.
  • 27. Li Z et al. MicroRNA dysregulation in uveal melanoma: a new player enters the game. Oncotarget 2015;6(7):4562-8.
  • 28. Zhang B et al. microRNAs as oncogenes and tumor suppressors. Dev Biol 2007;302(1):1-12.
  • 29. Aughton K, Kalirai H., Coupland SE. MicroRNAs and Uveal Melanoma: Understanding the Diverse Role of These Small Molecular Regulators. Int J Mol Sci 2020;21(16):5648.
  • 30. Catalanotto C, Cogoni C, Zardo G. MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions. Int J Mol Sci 2016;17(10):1712.
  • 31. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004;5(7):522-31.
  • 32.Erson AE, Petty EM. miRNAs and cancer: New research developments and potential clinical applications. Cancer Biol Ther 2009;8(24):2317-22.
  • 33.Lagana A et al. Variability in the incidence of miRNAs and genes in fragile sites and the role of repeats and CpG islands in the distribution of genetic material. PLoS One 2010;5(6):e11166.
  • 34.Lamy P et al. Are microRNAs located in genomic regions associated with cancer? Br J Cancer 2006;95(10):1415-8.
  • 35.Yanqing Li, Yan Jiao, Zhuo Fu, Zhangping Luo, Jing Su, and Yang Li., High miR-454-3p expression predicts poor prognosis in hepatocellular carcinoma. Cancer Manag Res. 2019; 11: 2795–802.
  • 36.Song Y, Guo Q, Gao S, Hua K. MiR-454-3p promotes proliferation and induces apoptosis in human cervical cancer cells by targeting TRIM3. Biochemical and Biophysical Research Communications 2019;516(3):872-9.
  • 37.Liangliang R, Han C, Junwei S, Xuhong C, Chun L, Xiaolan Z, Ning H et al. MiR-454-3p-Mediated Wnt/β-catenin Signaling Antagonists Suppression Promotes Breast Cancer Metastasis. Theranostics 2019;9(2):449–65.
  • 38.Naiyuan S, Lei W, Lian X, Rong W, Qing L. Plasma miR-454-3p as a potential prognostic indicator in human glioma. Neurological Sciences 2015;36:309–13.
  • 39. Eedunuri VK et al. miR-137 Targets p160 Steroid Receptor Coactivators SRC1, SRC2, and SRC3 and Inhibits Cell Proliferation. Mol Endocrinol 2015;29(8):1170-83.
  • 40.Li Y et al. MicroRNA 145 may play an important role in uveal melanoma cell growth by potentially targeting insulin receptor substrate-1. Chin Med J (Engl) 2014;127(8):1410-6.
  • 41.Sun L et al. MiR-144 Inhibits Uveal Melanoma Cell Proliferation and Invasion by Regulating c-Met Expression. PLoS One 2015;10(5):e0124428.
  • 42.Venza M et al. miR-92a-3p and MYCBP2 are involved in MS-275- induced and c-myc-mediated TRAIL-sensitivity in melanoma cells. Int Immunopharmacol 2016;40:235-43.
  • 43. Wang X et al. Coordinated targeting of MMP-2/MMP-9 by miR- 296-3p/FOXCUT exerts tumor-suppressing effects in choroidal malignant melanoma. Mol Cell Biochem 2018;445(1-2):25-33.
  • 44. Zhou J et al. Oncogenic role of microRNA20a in human uveal melanoma. Mol Med Rep 2016;14(2):1560-6.
  • 45. Ling JW et al. miR-367 promotes uveal melanoma cell proliferation and migration by regulating PTEN. Genet Mol Res 2017;16(3). doi: 10.4238/gmr16039067.
  • 46. Li J et al. miR-224-5p inhibits proliferation, migration, and invasion by targeting PIK3R3/AKT3 in uveal melanoma. J Cell Biochem 2019;120(8):12412-21.
  • 47. Wang YC et al. Role of microRNA-21 in uveal melanoma cell invasion and metastasis by regulating p53 and its downstream protein. Int J Ophthalmol 2018;11(8):1258-68.
  • 48. Wang Y et al. Role of miR-23a/Zeb1 negative feedback loop in regulating epithelial-mesenchymal transition and tumorigenicity of intraocular tumors. Oncol Lett 2018;16(2):2462-70.
  • 49. Ilangumaran, S, Villalobos-Hernandez A, Bobbala, D, & Ramanathan, S. The hepatocyte growth factor (HGF)–MET receptor tyrosine kinase signaling pathway: Diverse roles in modulating immune cell functions. Cytokine 2016;82:125-39.

HIGH LEVEL OF miR-454 EXPRESSION IN SERUM/PLASMA OF UVEAL MALIGN MELANOM PATIENTS

Yıl 2022, Cilt: 5 Sayı: 1, 14 - 19, 10.02.2022
https://doi.org/10.26650/JARHS2022-981726

Öz

Objective: Uveal malignant melanoma (UMM) is a cancer type that has a poor prognosis and high metastasis tendency and is difficult to diagnose early. Therefore, non-invasive diagnostic and prognostic markers are needed in this disease. In the study, it was investigated the expression level of miR-454 in serum /plasma samples of UMM patients and also evaluated the feature of a diagnostic and prognostic biomarker of miR-454. Material and Method: This study was performed on peripheral blood samples from 72 patients with UMM and 72 healthy controls matched for age, sex, and ethnicity, who applied to Istanbul University, Istanbul Faculty of Medicine, Department of Ophthalmology and Oncology Institute. MicroRNA-454 expression level in cell-free RNA (cfRNA) isolated from serum/plasma was investigated by the Real-Time PCR (RT-PCR). The expression level of miR-454 determined according to the reference gene was evaluated by comparing it with patients and healthy controls. Results: It was found that the expression level of miR-454 increased 4.14 times in the patient group compared to the healthy controls, and it was statistically significant. In the study, it was shown that there is a significant relationship between miR-454 expression level and smoking and alcohol intake. When the mRNAs targeted by the miR-454 molecule were examined via bioinformatic tools and, it was understood that the relevant miRNA had a repressing feature and accordingly assumed the role of an oncogene. Conclusion: Our study has shown that miR-454, which was previously reported to have high expression levels in cell lines and UMM tumor tissue, is also found at high levels in the serum/plasma of UMM patients. The results suggest that miR-454 can be a diagnostic and prognostic biomarker in uveal malignant melanoma and can be considered as a important therapeutic target.

Proje Numarası

Proje No: TDK-2019-35336

Kaynakça

  • 1. Krantz BA et al. Uveal melanoma: epidemiology, etiology, and treatment of primary disease. Clin Ophthalmol 2017;11:279-89.
  • 2. Shields CL et al. American Joint Committee on Cancer classification of posterior uveal melanoma (tumor size category) predicts prognosis in 7731 patients. Ophthalmology 2013;120(10):2066-71.
  • 3. Shields JA, Shields CL. Management of posterior uveal melanoma: past, present, and future: the 2014 Charles L. Schepens lecture. Ophthalmology 2015;122(2):414-28.
  • 4. Eskelin S et al. Tumor doubling times in metastatic malignant melanoma of the uvea: tumor progression before and after treatment. Ophthalmology 2000;107(8):1443-9.
  • 5. Materin MA, Faries M, Kluger HM. Molecular alternations in uveal melanoma. Curr Probl Cancer 2011;35(4):211-24.
  • 6. Dithmar S, Diaz CE, Grossniklaus HE. Intraocular melanoma spread to regional lymph nodes: report of two cases. Retina 2000;20(1):76-9.
  • 7. Koc I, Kiratli H. Current Management of Conjunctival Melanoma Part 2: Treatment and Future Directions. Turk J Ophthalmol 2020;50(6):362-70.
  • 8. Wong JR et al. Management of conjunctival malignant melanoma: a review and update. Expert Rev Ophthalmol 2014;9(3):185-204.
  • 9. Seregard S. Conjunctival melanoma. Surv Ophthalmol 1998;42(4):321-50.
  • 10. Brownstein S. Malignant melanoma of the conjunctiva. Cancer Control 2004;11(5):310-6.
  • 11. Kujala E, Makitie T, Kivela T. Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci 2003;44(11):4651-9.
  • 12. Sun L et al. MicroRNA-454 functions as an oncogene by regulating PTEN in uveal melanoma. FEBS Lett 2015;589(19 Pt B):2791-6.
  • 13. McLaughlin CC et al. Incidence of noncutaneous melanomas in the U.S. Cancer 2005;103(5):1000-7.
  • 14. Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1998;83(8):1664-78.
  • 15. Johansson CC et al. Expression and prognostic significance of iNOS in uveal melanoma. Int J Cancer 2010;126(11):2682-9.
  • 16. Yan D et al. MicroRNA-34a inhibits uveal melanoma cell proliferation and migration through downregulation of c-Met. Invest Ophthalmol Vis Sci 2009;50(4):1559-65.
  • 17. Chen X et al. Epigenetics, microRNAs, and carcinogenesis: functional role of microRNA-137 in uveal melanoma. Invest Ophthalmol Vis Sci 2011;52(3):1193-9.
  • 18. Singh AD, Shields CL, Shields JA. Prognostic factors in uveal melanoma. Melanoma Res 2001;11(3):255-63.
  • 19. Chen X et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008;18(10):997-1006.
  • 20. Gilad S et al. Serum microRNAs are promising novel biomarkers. PLoS One 2008;3(9):e3148.
  • 21. Mitchell PS et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008;105(30):10513-8.
  • 22. Bignotti E et al. Identification of stably expressed reference small non-coding RNAs for microRNA quantification in high-grade serous ovarian carcinoma tissues. J Cell Mol Med 2016;20(12):2341-8.
  • 23. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116(2):281-97.
  • 24. Yi Fan Li, Li Dong, Yang Li, and Wen Bin Wei. A Review of MicroRNA in Uveal Melanoma. Onco Targets Ther 2020;13:6351–9.
  • 25. Zhang L et al. The miR-181 family promotes cell cycle by targeting CTDSPL, a phosphatase-like tumor suppressor in uveal melanoma. J Exp Clin Cancer Res 2018;37(1):15.
  • 26. Peng J, Liu H, Liu C. MiR-155 Promotes Uveal Melanoma Cell Proliferation and Invasion by Regulating NDFIP1 Expression. Technol Cancer Res Treat 2017;16(6):1160-7.
  • 27. Li Z et al. MicroRNA dysregulation in uveal melanoma: a new player enters the game. Oncotarget 2015;6(7):4562-8.
  • 28. Zhang B et al. microRNAs as oncogenes and tumor suppressors. Dev Biol 2007;302(1):1-12.
  • 29. Aughton K, Kalirai H., Coupland SE. MicroRNAs and Uveal Melanoma: Understanding the Diverse Role of These Small Molecular Regulators. Int J Mol Sci 2020;21(16):5648.
  • 30. Catalanotto C, Cogoni C, Zardo G. MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions. Int J Mol Sci 2016;17(10):1712.
  • 31. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004;5(7):522-31.
  • 32.Erson AE, Petty EM. miRNAs and cancer: New research developments and potential clinical applications. Cancer Biol Ther 2009;8(24):2317-22.
  • 33.Lagana A et al. Variability in the incidence of miRNAs and genes in fragile sites and the role of repeats and CpG islands in the distribution of genetic material. PLoS One 2010;5(6):e11166.
  • 34.Lamy P et al. Are microRNAs located in genomic regions associated with cancer? Br J Cancer 2006;95(10):1415-8.
  • 35.Yanqing Li, Yan Jiao, Zhuo Fu, Zhangping Luo, Jing Su, and Yang Li., High miR-454-3p expression predicts poor prognosis in hepatocellular carcinoma. Cancer Manag Res. 2019; 11: 2795–802.
  • 36.Song Y, Guo Q, Gao S, Hua K. MiR-454-3p promotes proliferation and induces apoptosis in human cervical cancer cells by targeting TRIM3. Biochemical and Biophysical Research Communications 2019;516(3):872-9.
  • 37.Liangliang R, Han C, Junwei S, Xuhong C, Chun L, Xiaolan Z, Ning H et al. MiR-454-3p-Mediated Wnt/β-catenin Signaling Antagonists Suppression Promotes Breast Cancer Metastasis. Theranostics 2019;9(2):449–65.
  • 38.Naiyuan S, Lei W, Lian X, Rong W, Qing L. Plasma miR-454-3p as a potential prognostic indicator in human glioma. Neurological Sciences 2015;36:309–13.
  • 39. Eedunuri VK et al. miR-137 Targets p160 Steroid Receptor Coactivators SRC1, SRC2, and SRC3 and Inhibits Cell Proliferation. Mol Endocrinol 2015;29(8):1170-83.
  • 40.Li Y et al. MicroRNA 145 may play an important role in uveal melanoma cell growth by potentially targeting insulin receptor substrate-1. Chin Med J (Engl) 2014;127(8):1410-6.
  • 41.Sun L et al. MiR-144 Inhibits Uveal Melanoma Cell Proliferation and Invasion by Regulating c-Met Expression. PLoS One 2015;10(5):e0124428.
  • 42.Venza M et al. miR-92a-3p and MYCBP2 are involved in MS-275- induced and c-myc-mediated TRAIL-sensitivity in melanoma cells. Int Immunopharmacol 2016;40:235-43.
  • 43. Wang X et al. Coordinated targeting of MMP-2/MMP-9 by miR- 296-3p/FOXCUT exerts tumor-suppressing effects in choroidal malignant melanoma. Mol Cell Biochem 2018;445(1-2):25-33.
  • 44. Zhou J et al. Oncogenic role of microRNA20a in human uveal melanoma. Mol Med Rep 2016;14(2):1560-6.
  • 45. Ling JW et al. miR-367 promotes uveal melanoma cell proliferation and migration by regulating PTEN. Genet Mol Res 2017;16(3). doi: 10.4238/gmr16039067.
  • 46. Li J et al. miR-224-5p inhibits proliferation, migration, and invasion by targeting PIK3R3/AKT3 in uveal melanoma. J Cell Biochem 2019;120(8):12412-21.
  • 47. Wang YC et al. Role of microRNA-21 in uveal melanoma cell invasion and metastasis by regulating p53 and its downstream protein. Int J Ophthalmol 2018;11(8):1258-68.
  • 48. Wang Y et al. Role of miR-23a/Zeb1 negative feedback loop in regulating epithelial-mesenchymal transition and tumorigenicity of intraocular tumors. Oncol Lett 2018;16(2):2462-70.
  • 49. Ilangumaran, S, Villalobos-Hernandez A, Bobbala, D, & Ramanathan, S. The hepatocyte growth factor (HGF)–MET receptor tyrosine kinase signaling pathway: Diverse roles in modulating immune cell functions. Cytokine 2016;82:125-39.
Toplam 49 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Klinik Tıp Bilimleri
Bölüm Araştırma Makaleleri
Yazarlar

Masoumeh Hassani 0000-0001-8976-4450

Demet Akdeniz Bu kişi benim 0000-0002-2271-8481

Tunay Doğan 0000-0001-5281-7360

Samuray Tuncer Bu kişi benim 0000-0001-7491-8613

Hülya Yazıcı 0000-0002-8919-0482

Proje Numarası Proje No: TDK-2019-35336
Erken Görünüm Tarihi 20 Ekim 2021
Yayımlanma Tarihi 10 Şubat 2022
Gönderilme Tarihi 12 Ağustos 2021
Yayımlandığı Sayı Yıl 2022 Cilt: 5 Sayı: 1

Kaynak Göster

MLA Hassani, Masoumeh vd. “UVEAL MALIGN MELANOMA HASTALARININ SERUM/ PLAZMASINDA YÜKSEK MiR-454 EKSPRESYONU”. Sağlık Bilimlerinde İleri Araştırmalar Dergisi, c. 5, sy. 1, 2022, ss. 14-19, doi:10.26650/JARHS2022-981726.