Estimation of miRNA-183 expression and TGF-β level in Chronic Myeloid Leukemia

Abstract

Background: MicroRNA-183 and Transforming Growth Factor Beta (TGF-β) have emerged as significant players in the pathophysiology of Chronic Myeloid Leukemia (CML). Research indicates that miRNA-183 may play a role in the regulation of cell proliferation and apoptosis in CML cells, potentially influencing disease progression and response to therapy. Elevated levels of miRNA-183 have been associated with poor prognosis, suggesting it could serve as a biomarker for disease severity.

Objective: In this study, we aimed to analyze the expression of miR-183 and TGF- β level and investigate the relationship between miR-183 and level of TGF- β in CML patients.

Material and Methods: The study has been carried out on 60 Iraqi patients (37 males and 23 females at age range 17 - 69 year) with chronic myeloid leukemia at chronic phase, who are referred to the National Center of Hematology/ Mustansiriyah University, Baghdad during the period from January to November 2023. Twenty of them are newly diagnosed (T0), and the other 40 patients are under treatment with TKIs (T+), Thirty age and gender-matched healthy subjects were  enrolled to act as control group. TGF-β level estimates by ELISA while micrRNA-183 detection using RT- PCR.

Conclusion: The elevated levels of TGF-β and miRNA-183 in CML patients, coupled with their positive correlation.

Keywords:

CML, imatinib, nilotinib, miRNA-183 and TGF-β

References

Rudich A, Garzon R, Dorrance A. Non-Coding RNAs Are Implicit in Chronic Myeloid Leukemia Therapy Resistance. Int J Mol Sci 2022, Vol 23, Page 12271 [Internet]. 2022 Oct 14 [cited 2024 Oct 10];23(20):12271. Available from: https://www.mdpi.com/1422-0067/23/20/12271/htm

Patterson SD, Copland M. The Bone Marrow Immune Microenvironment in CML: Treatment Responses, Treatment-Free Remission, and Therapeutic Vulnerabilities. Curr Hematol Malig Rep [Internet]. 2023 Apr 1 [cited 2024 Oct 12];18(2):19–32. Available from: https://link.springer.com/article/10.1007/s11899-023-00688-6

Osman AEG, Deininger MW. Chronic Myeloid Leukemia: Modern therapies, current challenges and future directions. Blood Rev. 2021 Sep 1;49:100825.

Singh P. MicroRNA based combinatorial therapy against TKIs resistant CML by inactivating the PI3K/Akt/mTOR pathway: a review. Med Oncol [Internet]. 2023 Oct 1 [cited 2024 Oct 10];40(10):1–15. Available from: https://link.springer.com/article/10.1007/s12032-023-02161-z

Gaál Z. Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation. Int J Mol Sci 2022, Vol 23, Page 5838 [Internet]. 2022 May 23 [cited 2022 Aug 30];23(10):5838. Available from: https://www.mdpi.com/1422-0067/23/10/5838/htm

Hameed AM, Amira Z, Al-Alwany SHM, Mtashar BA. Biochemical and breakpoint cluster region-c-ABL oncogene 1 polymorphism study among Iraqi patients with chronic myeloid leukemia. Iraqi J Hematol [Internet]. 2023 [cited 2024 Oct 12];12(2):176–83. Available from: https://journals.lww.com/ijhm/fulltext/2023/12020/biochemical_and_breakpoint_cluster_region_c_abl.10.aspx

Anelli L, Zagaria A, Specchia G, Musto P, Albano F. Dysregulation of miRNA in Leukemia: Exploiting miRNA Expression Profiles as Biomarkers. Int J Mol Sci 2021, Vol 22, Page 7156 [Internet]. 2021 Jul 2 [cited 2024 Oct 10];22(13):7156. Available from: https://www.mdpi.com/1422-0067/22/13/7156/htm

Wang X, Zuo D, Yuan Y, Yang X, Hong Z, Zhang R. MicroRNA-183 promotes cell proliferation via regulating programmed cell death 6 in pediatric acute myeloid leukemia. J Cancer Res Clin Oncol 2016 1431 [Internet]. 2016 Oct 13 [cited 2022 Aug 30];143(1):169–80. Available from: https://link.springer.com/article/10.1007/s00432-016-2277-2

Li H, Kloosterman W, Fekete DM. MicroRNA-183 Family Members Regulate Sensorineural Fates in the Inner Ear. J Neurosci [Internet]. 2010 Mar 3 [cited 2024 Oct 12];30(9):3254–63. Available from: https://www.jneurosci.org/content/30/9/3254

Li S, Meng W, Guo Z, Liu M, He Y, Li Y, et al. The miR-183 Cluster: Biogenesis, Functions, and Cell Communication via Exosomes in Cancer. Cells 2023, Vol 12, Page 1315 [Internet]. 2023 May 5 [cited 2024 Oct 10];12(9):1315. Available from: https://www.mdpi.com/2073-4409/12/9/1315/htm

Wosniaki DK, Marin AM, Oliveira RN, Koerich GM, Munhoz EC, Farias JS de H, et al. The Screening of microRNAs in Chronic Myeloid Leukemia: A Clinical Evaluation. Int J Mol Sci 2024, Vol 25, Page 3363 [Internet]. 2024 Mar 16 [cited 2024 Oct 10];25(6):3363. Available from: https://www.mdpi.com/1422-0067/25/6/3363/htm

Donatelli SS, Zhou JM, Gilvary DL, Eksioglu EA, Chen X, Cress WD, et al. TGF-β-inducible microRNA-183 silences tumor-associated natural killer cells. Proc Natl Acad Sci U S A [Internet]. 2014 Mar 18 [cited 2024 Oct 10];111(11):4203–8. Available from: https://www.pnas.org/doi/abs/10.1073/pnas.1319269111

Shabeeb Z, Faraj Y, Mahmood M, Mtashar B. Interplaying of regulatory T-cells and related chemokines in immune thrombocytopenic purpura patients. Iraqi J Hematol [Internet]. 2020 [cited 2024 Oct 12];9(2):138. Available from: https://journals.lww.com/ijhm/fulltext/2020/09020/interplaying_of_regulatory_t_cells_and_related.17.aspx

Abel Y, Rederstorff M. Stem-Loop qRT-PCR–Based Quantification of miRNAs. Methods Mol Biol [Internet]. 2021 [cited 2022 Apr 10];2300:59–64. Available from: https://link.springer.com/protocol/10.1007/978-1-0716-1386-3_6

Rao X, Huang X, Zhou Z, Lin X. An improvement of the 2ˆ(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. Biostat Bioinforma Biomath [Internet]. 2013 [cited 2022 Apr 15];3(3):71–85. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25558171%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4280562

Kim BG, Malek E, Choi SH, Ignatz-Hoover JJ, Driscoll JJ. Novel therapies emerging in oncology to target the TGF-β pathway. J Hematol Oncol 2021 141 [Internet]. 2021 Apr 6 [cited 2024 Oct 11];14(1):1–20. Available from: https://link.springer.com/articles/10.1186/s13045-021-01053-x

Castriconi R, Dondero A, Bellora F, Moretta L, Castellano A, Locatelli F, et al. Neuroblastoma-Derived TGF-β1 Modulates the Chemokine Receptor Repertoire of Human Resting NK Cells. J Immunol [Internet]. 2013 May 15 [cited 2022 May 23];190(10):5321–8. Available from: https://www.jimmunol.org/content/190/10/5321

Tie Y, Tang F, Peng D, Zhang Y, Shi H. TGF-beta signal transduction: biology, function and therapy for diseases. Mol Biomed 2022 31 [Internet]. 2022 Dec 19 [cited 2024 Oct 11];3(1):1–29. Available from: https://link.springer.com/article/10.1186/s43556-022-00109-9

Zhao H, Wei J, Sun J. Roles of TGF-β signaling pathway in tumor microenvirionment and cancer therapy. Int Immunopharmacol. 2020 Dec 1;89:107101.

Pendse S, Chavan S, Kale V, Vaidya A. A comprehensive analysis of cell-autonomous and non-cell-autonomous regulation of myeloid leukemic cells: The prospect of developing novel niche-targeting therapies. Cell Biol Int [Internet]. 2023 Oct 1 [cited 2024 Oct 12];47(10):1667–83. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/cbin.12078

Minciacchi VR, Kumar R, Krause DS. Chronic Myeloid Leukemia: A Model Disease of the Past, Present and Future. Cells 2021, Vol 10, Page 117 [Internet]. 2021 Jan 10 [cited 2024 Oct 11];10(1):117. Available from: https://www.mdpi.com/2073-4409/10/1/117/htm

Wu W, He X, Kong J, Ye B. Mir-373 affects human lung cancer cells’ growth and its E-cadherin expression. Oncol Res [Internet]. 2012 Jan 1 [cited 2024 Oct 11];20(4):163–70. Available from: https://europepmc.org/article/med/23461063

Mehta A, Baltimore D. MicroRNAs as regulatory elements in immune system logic. Nat Rev Immunol 2016 165 [Internet]. 2016 Apr 28 [cited 2022 May 23];16(5):279–94. Available from: https://www.nature.com/articles/nri.2016.40

Cao D, Di M, Liang J, Shi S, Tan Q, Wang Z. MicroRNA-183 in Cancer Progression. J Cancer [Internet]. 2020 [cited 2024 Oct 11];11(6):1315. Available from: /pmc/articles/PMC6995398/

Bugide S, Janostiak R, Wajapeyee N. Epigenetic Mechanisms Dictating Eradication of Cancer by Natural Killer Cells. Vol. 4, Trends in Cancer. Cell Press; 2018. p. 553–66.

Pesce S, Greppi M, Ferretti E, Obino V, Carlomagno S, Rutigliani M, et al. miRNAs in NK Cell-Based Immune Responses and Cancer Immunotherapy. Front Cell Dev Biol [Internet]. 2020 Feb 25 [cited 2021 Oct 10];8. Available from: /pmc/articles/PMC7053181/.