The Change in Expression Levels of RYBP and MDM2 Genes in Colorectal Cancer

Abstract

Objective: Colorectal cancer, frequently seen among gastrointestinal cancers, is one of the major causes in mortality and morbidity worldwide. In this study, we aimed to investigate the expression levels of RYBP and MDM2 genes in colorectal cancer. We further examined the possible correlation between RYBP and MDM2 expressions in colorectal cancer and the relationship between the expression of these genes and the clinicopathological features of patients with colorectal cancer. Materials and Methods: In this study, fresh tumor colon/rectum tissues and the adjacent healthy tissues collected from 43 patients with colorectal cancer during a surgical operation. RYBP and MDM2 mRNA expressions were examined using Real-Time PCR. Results: In this study results showed that the expression levels of both RYBP and MDM2 were decreased in tumor tissues compared to normal tissues with colorectal cancer patients, but these decreases were not statistically significant (p=0.673 and p=0.721, respectively). Moreover, while there was no correlation between RYBP and MDM2 mRNA expressions in colorectal cancer, no statistically significant relationship was found between the expressions of these genes and clinicopathological data (p>0.05). Conclusion: Consequently, it can be said that RYBP and MDM2 expressions are not related to colorectal cancer, however, future studies with larger sample groups are needed to validate the results obtained from this study.

Keywords

• Colorectal cancer
• Gene Expression
• RYBP
• MDM2
• Real-Time PCR

Project Number

FEF.YLT.17.13

Kolorektal Kanserde RYBP ve MDM2 Genlerinin Ekspresyon Düzeylerindeki Değişimi

Abstract

Giriş ve Amaç: Gastrointestinal kanserler arasında sıklıkla görülen kolorektal kanser, dünya genelinde mortalite ve morbiditenin en önemli nedenlerinden biridir. Bu çalışmada kolorektal kanserde RYBP ve MDM2 genlerinin ekspresyon düzeylerini araştırmayı amaçladık. Ayrıca kolorektal kanserde RYBP ve MDM2 ekspresyonları arasındaki olası korelasyonu ve bu genlerin ekspresyonu ile kolorektal kanserli hastaların klinikopatolojik özellikleri arasındaki ilişkiyi inceledik. Gereç ve Yöntemler: Bu çalışmada, cerrahi operasyon sonucunda 43 kolorektal kanserli hastanın tümörlü kolon/rektum dokuları ve komşu sağlıklı dokuları toplandı. RYBP ve MDM2 mRNA ekspresyonları Real-Time PCR kullanılarak incelendi. Bulgular: Çalışmanın sonucunda tümörlü dokularda normal dokulara kıyasla hem RYBP hem de MDM2 ekspresyonlarında azalış görüldü fakat bu azalış istatistiksel açıdan anlamlı değildi (sırasıyla p=0.673 ve p=0.721). Ayrıca kolorektal kanserde RYBP ve MDM2 mRNA ekspresyonları arasında korelasyon bulunmazken, bu genlerin ekspresyonları ile klinikopatolojik veriler arasında istatistiksel olarak anlamlı bir ilişki saptanmadı (p>0.05). Sonuç: Sonuç olarak, RYBP ve MDM2 ekspresyonlarının kolorektal kanser ile ilişkili olmadığı söylenebilir, ancak bu çalışmadan elde edilen sonuçları doğrulamak için daha büyük örneklem grupları ile yapılacak çalışmalara ihtiyaç vardır.

Keywords

• Kolorektal kanser
• Gen ekspresyonu
• RYBP
• MDM2
• Real-Time PCR

Supporting Institution

Gaziantep Üniversitesi Bilimsel Araştırma Projeleri Birimi

Project Number

FEF.YLT.17.13

Thanks

Çalışmaya sağladığı finansal destekten dolayı Gaziantep Üniversitesi Bilimsel Araştırma Projeleri Birimi'ne teşekkür ederiz.

References

1. 1. Keum, N, Giovannucci, E, Global burden of colorectal cancer:emerging trends, risk factors and prevention strategies, Nature Reviews Gastroenterology & Hepatology, 2019,16, 713-32.
2. 2. Rawla, P, Sunkara, T, Barsouk, A, Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors, Gastroenterology Review, 2019, 14(2), 89-103.
3. 3. Dekker, E, Tanis, P.J, Vleugels, J.L.A, Kasi, P.M, Wallace, M.B, Colorectal cancer, Lancet, 2019, 394, 1467-80.
4. 4. Martinez, A.M, Cavalli, G, The role of polycomb group proteins in cell cycle regulation during development, Cell Cycle, 2006, 5(1), 1189-97.
5. 5. Wang, W, Cheng, J, Qin, J.J, Voruganti, S, Nag, S, Fan, Gao, Q, Zhang, R, RYBP expression is associated with better survival of patients with hepatocellular carcinoma (HCC) and responsiveness to chemotherapy of HCC cells in vitro and in vivo, Oncotarget, 2014, 5, 11604-19.
6. 6. Zhan, S, Wang, T, Ge, W, Li, J. Multiple roles of Ring 1 and YY1 binding protein in physiology and disease, Journal of Cellular and Molecular Medicine, 2018, 22(4), 2046-54.
7. 7. Lando, M, Wilting, S.M, Snipstad, K, Clancy, T, Bierkens, M, Aarnes, E.K, Holden, M, Stokke, T, Sundfør, K, Holm, R, Kristensen, G.B, Steenbergen, R.D, Lyng, H, Identification of eight candidate target genes of the recurrent 3p12-p14 loss in cervical cancer by integrative genomic profiling, The Journal of Pathology, 2013, 230(1), 59-69.
8. 8. Krohn, A, Seidel, A, Burkhardt, L, Bachmann, F, Mader, M, Grupp, K, Eichenauer, T, Becker, A, Adam, M, Graefen, M, Huland, H, Kurtz, S, Steurer, S, Tsourlakis, M.C, Minner, S, Michl, U, Schlomm, T, Sauter, G, Simon, R, Sirma, H, Recurrent deletion of 3p13 targets multiple tumour suppressor genes and defines a distinct subgroup of aggressive ERG fusion‐positive prostate cancers, The Journal of Pathology, 2013, 231(1), 130-41.

9. 9. Zhu, X, Yan, M, Luo, W, Liu, W, Ren, Y, Bei, C, Tang, G, Chen, R, Tan, S, Expression and clinical significance of PcG associated protein RYBP in hepatocellular carcinoma, Oncology Letters, 2017, 13, 141-50.
10. 10. Ke, Y, Guo, W, Huang, S, Li, Y, Guo, Y, Liu, X, Jin, Y, Ma, H, RYBP inhibits esophageal squamous cell carcinoma proliferation through downregulating CDC6 and CDC45 in G1-S phase transition process, Life Sciences, 2020, 250, 117578.
11. 11. Zhao, Y, Yu, H, Hu, W, The regulation of MDM2 oncogene and its impact on human cancers, Acta Biochimica et Biophysica Sinica, 2014, 46, 180-9.
12. 12. Liu, L, Yang, L, Chang, H, Chen, Y.N, Zhang, F, Feng, S, Peng, J, Ren C.C, Zhang X.A, CP 31398 attenuates endometrial cancer cell invasion, metastasis and resistance to apoptosis by downregulating MDM2 expression, International Journal of Oncology, 2019, 54, 942-54.
13. 13. Chen, D, Zhang, J, Li, M, Rayburn, E.R, Wang, H, Zhang, R, RYBP stabilizes p53 by modulating MDM2, EMBO Reports, 2009, 10(2), 166-72.
14. 14. Hou, H, Sun, D, Zhang, X, The role of MDM2 amplification and overexpression in therapeutic resistance of malignant tumors, Cancer Cell International, 2019, 19, 216.
15. 15. Arena, G, Riscal, R, Linares, L.K, Cam, L.L, MDM2 controls gene expression independently of p53 in both normal and cancer cells, Cell Death & Differentiation, 2018, 25, 1533-5.
16. 16. Freedman, D.A, Wu, L, Levine, A.J, Functions of the MDM2 oncoprotein, Cellular and Molecular Life Sciences, 1999, 55(1), 96-107.
17. 17. Polsky, D, Melzer, K, Hazan, C, Panageas, K.S, Busam, K, Drobnjak, M, Kamino, H, Spira, J.G, Kopf, A.W, Houghton, A, Cordon-Cardo, C, Osman, I, HDM2 protein overexpression and prognosis in primary malignant melanoma, Journal of the National Cancer Institute, 2002, 94, 1803-6.
18. 18. Lukas, J, Gao, D.Q, Kashmeshian, M, Wen, W.H, Tsao-Wei, D, Rosenberg, S, Press, M.F, Alternative and aberrant messenger RNA splicing of the Mdm2 oncogene in invasive breast cancer, Cancer Research, 2001, 61, 3212-9.
19. 19. Higashiyama, M, Doi, O, Kodama, K, Yokouchi, H, Kasugai, T, Ishiguro, S, Takami, K, Nakayama, T, Nishisho, I, MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation, British Journal of Cancer, 1997, 75, 1302-8.
20. 20. Chen, Y, Wang, D.D, Wu, Y.P, Su, D, Zhou, T.Y, Gai, R.H, Fu, Y, Zheng, L, He, Q.J, Zhu, H, Yang, B, MDM2 promotes epithelial-mesenchymal transition and metastasis of ovarian cancer SKOV3 cells, British Journal of Cancer, 2017, 117, 1192-201.
21. 21. Inomistova, M.V, Svergun, N.M, Khranovska, N.M, Skachkova, O.V, Gorbach, O.I, Klymnyuk, G.I, Prognastic significance of MDM2 gene expression in childhood neurobastoma, Experimental Oncology, 2015, 37(2), 111-5.
22. 22. Kriegmair, M.C, Balk, M, Wirtz, R, Steidler, A, Weis, C.A, Breyer, J, Hartmann, A, Bolenz, C, Erben, P, Expression of the p53 Inhibitors MDM2 and MDM4 as Outcome Predictor in Muscle-invasive Bladder Cancer, Anticancer Research, 2016, 36, 5205-14.
23. 23. Millon, R, Muller, D, Schultz, I, Salvi R, Ghnassia J.P, Frebourg, T, Wasylyk, B, Abecassis, J, Loss of MDM2 expression in human head and neck squamous cell carcinomas and clinical significance, Oral Oncology, 2001, 37, 620-31.
24. 24. Livak, K.J, Schmittgen, T.D, Analysis of relative gene expression data using real-time quantitative PCR and the 2-∆∆CT method, Methods, 2001, 25, 402-8.
25. 25. Gurer, T, Aytekin, A, Alahdab, Y, Arf6 expression in the tissues of patients with colorectal cancer. International Journal of Human Genetics, 2020, 20, 132-137.
26. 26. Sánchez-Beato, M, Sánchez, E, García, J, Pérez-Rosado, A, Montoya, M.C, Fraga, M, Artiga, M.J, Navarrete, M, Abraira, V, Morente, M, Esteller, M, Koseki, H, Vidal, M, Piris, M.A, Abnormal PcG protein expression in Hodgkin's lymphoma. Relation with E2F6 and NFκB transcription factors, The Journal of Pathology, 2004, 204(5), 528-37.
27. 27. Zhao, Q, Cai, W, Zhang, X, Tian, S, Zhang, J, Li, H, Hou, C, Ma, X, Chen, H, Huang, B, Chen D, RYBP Expression Is Regulated by KLF4 and Sp1 and Is Related Hepatocellular Carcinoma Prognosis, Journal of Biological Chemistry, 2017, 292(6), 2143-58.
28. 28. Zhou, L, Wang, L, Lu, L, Jiang, P, Sun, H, Wang, H, A novel target of microRNA-29, Ring1 and YY1-binding Protein (Rybp), negatively regulates skeletal myogenesis, Journal of Biological Chemistry, 2012, 287(30), 25255-65.
29. 29. Kondo, I, Iida, S, Takagi, Y, Sugihara, K, MDM2 mRNA expression in the p53 pathway may predict the potential of invasion and liver metastasis in colorectal cancer, Diseases of the Colon & Rectum, 2008, 51(9), 1395-402.
30. 30. Karni-Schmidt, O, Lokshin, M, Prives, C, The roles of MDM2 and MDMX in cancer, Annual Review of Pathology: Mechanisms of Disease, 2016, 11, 617-44.
31. 31. Coomer, A.O, Black, B, Greystoke, A, Munkley, J, Elliott, D.J, Alternative splicing in lung cancer, Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, 2019, 1862, 194388.
32. 32. Loo, L.W.M, Gao, C, Shvetsov. Y.B, Okoro, D.R, Hernandez, B.Y, Bargonetti, J, MDM2, MDM2-C, and mutant p53 expression influence breast cancer survival in a multiethnic population, Breast Cancer Research and Treatment, 2019, 174, 257-69.
33. 33. Evans, S.C, Viswanathan, M, Grier, J.D, Narayana, M, El-Naggar, A.K, Lozano, G, An alternatively spliced HDM2 product increases p53 activity by inhibiting HDM2, Oncogene, 2001, 20, 4041-9.
34. 34. Jing, X, Cai, W, Huang, B, Chen, H, Chen, D, Clinical significance of RYBP expression in primary hepatocellular carcinoma, Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2019, 44(4), 399-405.