[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
Main Menu
Home::
Journal Information::
Articles archive::
For Authors::
For Reviewers::
Registration::
Contact us::
Site Facilities::
Indexing & Abstracting::
Publication Ethics::
::
Search in website

Advanced Search
..
Receive site information
Enter your Email in the following box to receive the site news and information.
..
Indexing & Abstracting
DOAJ
GOOGLE SCHOLAR
..
:: Volume 28, Issue 3 (4-2023) ::
__Armaghane Danesh__ 2023, 28(3): 416-428 Back to browse issues page
Investigation of SMAD3 and SMAD4 Genes Expression in CML Patients and K562 Cell Line
T Mahdloo1 , HR Godarzi 2, M Jafarinia1
1- Department of Genetic, Marvdasht branch, Islamic Azad University, Marvdasht, Iran
2- Department of Genetic, Marvdasht branch, Islamic Azad University, Marvdasht, Iran , godarzih@alumni.tums.ac.ir
Abstract:   (578 Views)
Background & aim: Chronic myeloid leukemia or CML is a clonal myeloproliferative disorder with abnormal Philadelphia chromosome cytogenetic index. One of the important signaling pathways in the process of proliferation and apoptosis of cancer cells and disease pathogenesis is β-TGF, the dysregulation of the expression of its components, such as the SMAD family, plays a significant role in regulating tumor growth and cancer development. Therefore, the aim of the present study was to determine and investigate the expression of SMAD3 and SMAD4 genes in patients with CML and K562 cell line.
Methods: the present descriptive case-control study was conducted in 2020 at the Islamic Azad University, Marvdasht Branch. The statistical population of the research included 80 people who referred to the link and were divided into two groups; 40 patients with CML were selected as the case group and 40 healthy individuals as controls, matched in terms of age and sex, and K562 cell line. The expression levels of SMAD3 and SMAD4 genes were measured by Real Time PCR and cDNA synthesis, and the collected data were analyzed using one-way ANOVA T-test.
Results: The SMAD3 gene was significantly decreased in CML patients and this was as well observed in the K562 cell line (p<0.0001) and the level of SMAD4 gene expression in the patients and the K562 cell line did not display any significant relationship with the disease (p<0.0001). 0.001) P values less than 0.05 were considered.
Conclusion: According to the results of the present study, the expression of some genes in the signaling pathways can play an effective role in the development of disease or drug resistance. The decrease in SMAD3 expression in CML can indicate the relationship between the disease and the disorder in gene expression.
 
Keywords: CML, TGF- β, SMAD3, SMAD4
Full-Text [PDF 886 kb]   (137 Downloads)    
Type of Study: Research | Subject: Special
Received: 2022/12/27 | Accepted: 2023/03/13 | Published: 2023/05/6
References
1. Wang B, He F, Hu Y, Wang Q, Wang D, Sha Y, et al. Cancer incidence and mortality and risk factors in member countries of the " Belt and Road " initiative. BMC Cancer. 2022;22(1):582.## [DOI:10.1186/s12885-022-09657-3] [PMID] []
2. Koretzky GA. The legacy of the Philadelphia chromosome. J Clin Invest 2007; 117(8): 2030-2. ## [DOI:10.1172/JCI33032] [PMID] []
3. Grover A, Sanjuan-Pla A, Thongjuea S, Carrelha J, Giustacchini A, Gambardella A, et al. Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells. Nat Commun 2016; 7: 11075. ## [DOI:10.1038/ncomms11075] [PMID] []
4. Hamad A, Sahli Z, El-Sabban M, Mouteirik M, Nasr R. Emerging Therapeutic strategies for targeting chronic myeloid leukemia stem cells. Stem Cells International 2013; 2013: 724360. ## [DOI:10.1155/2013/724360] [PMID] []
5. Ribera JM. Philadelphia chromosome-like acute lymphoblastic leukemia. Still a pending matter. Haematologica 2021; 106(6): 1514-6. ## [DOI:10.3324/haematol.2020.270645] [PMID] []
6. Muffly L, Kebriaei P. Philadelphia chromosome positive acute lymphoblastic leukemia in adults: Therapeutic options and dilemmas in 2020. Semin Hematol 2020; 57(3): 137-41. ## [DOI:10.1053/j.seminhematol.2020.09.002] [PMID]
7. O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003; 348(11): 994-1004. ## [DOI:10.1056/NEJMoa022457] [PMID]
8. Xiao L, Yuan X, Sharkis SJ. Activin A maintains self-renewal and regulates fibroblast growth factor, Wnt, and bone morphogenic protein pathways in human embryonic stem cells. Stem Cells 2006; 24(6): 1476-86. ## [DOI:10.1634/stemcells.2005-0299] [PMID]
9. Derynck R, Turley SJ, Akhurst RJ. TGFbeta biology in cancer progression and immunotherapy. Nat Rev Clin Oncol 2021; 18(1): 9-34. ## [DOI:10.1038/s41571-020-0403-1] [PMID] []
10. Syed V. TGF-beta Signaling in Cancer. J Cell Biochem 2016; 117(6): 1279-87. ## [DOI:10.1002/jcb.25496] [PMID]
11. Dong M, Blobe GC. Role of transforming growth factor-beta in hematologic malignancies. Blood 2006; 107(12): 4589-96. ## [DOI:10.1182/blood-2005-10-4169] [PMID] []
12. Elkholy RA, Fouda MH, Elhawary EE, Elkholy RA, Elshora OA. Impact of CD105 flow-cytometric expression on childhood b-acute lymphoblastic leukemia. J Blood Med 2021; 12: 147-56. ## [DOI:10.2147/JBM.S300067] [PMID] []
13. Wrana JL, Attisano L, Wieser R, Ventura F, Massague J. Mechanism of activation of the TGF-beta receptor. Nature 1994; 370(6488): 341-7. ## [DOI:10.1038/370341a0] [PMID]
14. Massague J, Wotton D. Transcriptional control by the TGF-beta/Smad signaling system. EMBO J 2000; 19(8): 1745-54. ## [DOI:10.1093/emboj/19.8.1745] [PMID] []
15. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003; 425(6958): 577-84. ## [DOI:10.1038/nature02006] [PMID]
16. Imai Y, Kurokawa M, Izutsu K, Hangaishi A, Maki K, Ogawa S, et al. Mutations of the Smad4 gene in acute myelogeneous leukemia and their functional implications in leukemogenesis. Oncogene 2001; 20(1): 88-96. ## [DOI:10.1038/sj.onc.1204057] [PMID]
17. Moustakas A, Souchelnytskyi S, Heldin CH. Smad regulation in TGF-beta signal transduction. J Cell Sci 2001; 114(24): 4359-69. ## [DOI:10.1242/jcs.114.24.4359] [PMID]
18. Li Z, Li J, Shan X, Gui S, Li C, Zhang Y. Expression of transforming growth factor beta1, smad3, and phospho-smad3 in somatotropinomas and their relationship to tumor behavior. World Neurosurg 2021; 153: e20-e7. ## [DOI:10.1016/j.wneu.2021.05.088] [PMID]
19. Massague JXi Q. TGF-beta control of stem cell differentiation genes. FEBS Lett 2012; 586(14): 1953-8. ## [DOI:10.1016/j.febslet.2012.03.023] [PMID] []
20. Shi X, DiRenzo D, Guo LW, Franco SR, Wang B, Seedial S, et al. TGF-beta/Smad3 stimulates stem cell/developmental gene expression and vascular smooth muscle cell de-differentiation. PLoS One 2014; 9(4): e93995. ## [DOI:10.1371/journal.pone.0093995] [PMID] []
21. Tefferi A. Classification, diagnosis and management of myeloproliferative disorders in the JAK2V617F era. Hematology Am Soc Hematol Educ Program 2006;:240-5. ## [DOI:10.1182/asheducation-2006.1.240] [PMID]
22. Zhao M, Mishra L, Deng CX. The role of TGF-beta/SMAD4 signaling in cancer. Int J Biol Sci 2018; 14(2): 111-23. ## [DOI:10.7150/ijbs.23230] [PMID] []
23. Roelen BA, Cohen OS, Raychowdhury MK, Chadee DN, Zhang Y, Kyriakis JM, et al. Phosphorylation of threonine 276 in Smad4 is involved in transforming growth factor-beta-induced nuclear accumulation. Am J Physiol Cell Physiol 2003; 285(4): C823-30. ## [DOI:10.1152/ajpcell.00053.2003] [PMID]
24. Zhang Y, Musci T, Derynck R. The tumor suppressor Smad4/DPC 4 as a central mediator of Smad function. Curr Biol 1997; 7(4): 270-6. ## [DOI:10.1016/S0960-9822(06)00123-0] [PMID]
25. Shokeen Y, Sharma NR, Vats A, Dinand V, Beg MA, Sanskaran S, et al. Association between altered expression and genetic variations of transforming growth factor beta-smad pathway with chronic myeloid leukemia. Int J Hematol Oncol Stem Cell Res 2018; 12(1): 14-22. ##
26. Andreeff M, Wang R-y, Davis RE, Jacamo R, Ruvolo PP, McQueen T, et al. Proteomic, Gene expression, and micro-rna analysis of bone marrow mesenchymal stromal cells in acute myeloid leukemia identifies pro-inflammatory, pro-survival signatures in vitro and in vivo. Blood 2013; 2(21): 3685-## [DOI:10.1182/blood.V122.21.3685.3685]
27. Singh P, Srinivasan R, Wig JD, Radotra BD. A study of Smad4, Smad6 and Smad7 in surgically resected samples of pancreatic ductal adenocarcinoma and their correlation with clinicopathological parameters and patient survival. BMC Res Notes 2011; 4: 460. ## [DOI:10.1186/1756-0500-4-560] [PMID] []
28. Bailey KL, Agarwal E, Chowdhury S, Luo J, Brattain MG, Black JD, et al. TGFbeta/Smad3 regulates proliferation and apoptosis through IRS-1 inhibition in colon cancer cells. PLoS One 2017; 12(4): e0176096. ## [DOI:10.1371/journal.pone.0176096] [PMID] []
29. 29Zhang J, Zhang M, Liang Y, Liu M, Huang Z. Downregulation of Smad4 expression confers chemoresistance against imatinib mesylate to chronic myeloid leukemia K562 cells. Hematology 2022; 27(1): 43-52. ## [DOI:10.1080/16078454.2021.2010331] [PMID]
30. Alazzouzi H, Alhopuro P, Salovaara R, Sammalkorpi H, Jarvinen H, Mecklin JP, et al. SMAD4 as a prognostic marker in colorectal cancer. Clin Cancer Res 2005; 11(7): 2606-11. ## [DOI:10.1158/1078-0432.CCR-04-1458] [PMID]
Send email to the article author

Add your comments about this article
Your username or Email:

CAPTCHA



XML   Persian Abstract   Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Mahdloo T, Godarzi H, Jafarinia M. Investigation of SMAD3 and SMAD4 Genes Expression in CML Patients and K562 Cell Line. armaghanj 2023; 28 (3) :416-428
URL: http://armaghanj.yums.ac.ir/article-1-3418-en.html


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 28, Issue 3 (4-2023) Back to browse issues page
ارمغان دانش Armaghane Danesh
Persian site map - English site map - Created in 0.05 seconds with 39 queries by YEKTAWEB 4645