The study of Relationship between Dysregulation of RP11-446E9, HOTAIR, and P21 Long non-coding RNA and Acute Lymphocytic Leukemia Patients
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Abstract
Acute lymphoblastic leukemia is a kind of hematological cancer resulting from the aberrant proliferation of immature lymphoid cells. Recently discovered lncRNAs longer than 200 nt interact with various cellular processes, including pluripotency and oncogenesis. Studies show that lncRNA expression profiles in ALL can serve as early diagnostic and prognostic indicators. The purpose of this work is to assess the lncRNA expression profile of three lncRNAs, including lncRNA RP11-446E9, lncRNA HOTAIR and lncRNA P21, in newly diagnosed ALL patients and controls, and to calculate the relationship between some blood parameters like, White blood cell count, hemoglobin and blood platelets and these three lncRNA expression patterns, as well as to determine whether an association between the expression of lncRNAs RP11-446E9, HOTAIR, P21 expression and cluster of differentiation are occur or not. We obtained 30 patient blood samples for this investigation, with an equal number from healthy donors. We extracted total RNA from these samples and synthesized cDNA. We then assessed lncRNA expression levels by real-time PCR, with P-values <0.05 considered statistically significant. Our results showed that ALL samples had significantly higher expression levels of the lncRNAs RP11-446E9, HOTAIR, and P21 than healthy samples (P = 0.0218, p < 0.0001, p = 0.0252). Moreover, the relationships between these lncRNAs and Cluster of Differentiation markers and blood parameters varied. Dysregulation of lncRNAs in ALL samples offers promising potential for early diagnosis, prognosis, and treatment management.
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References
1. Mohsen AM, Ali ZA. Ceruloplasmin and some biochemical parameters as a marker for acute myeloid leukemic patients. Tikrit Journal of Pure Science. 2023;28(4):13-25. https://doi.org/10.25130/tjps.v28i4.1526
2. Thanoon SR, Abd Alrazzaq MN. Detecting Outliers in the Simple Linear Regression for Children Affected with Leukemia in Mosul City. Tikrit Journal of Pure Science. 2022;27(3). https://doi.org/10.25130/tjps.v27i3.47
3. Cruz-Miranda GM, Hidalgo-Miranda A, Bárcenas-López DA, Núñez-Enríquez JC, Ramírez-Bello J, Mejía-Aranguré JM, et al. Long non-coding RNA and acute leukemia. International journal of molecular sciences. 2019;20(3):735. https://doi.org/10.3390/ijms20030735
4. Aureli A, Marziani B, Venditti A, Sconocchia T, Sconocchia G. Acute lymphoblastic leukemia immunotherapy treatment: now, next, and beyond. Cancers. 2023;15(13):3346. https://doi.org/10.3390/cancers15133346
5. Hiam-Galvez KJ, Allen BM, Spitzer MH. Systemic immunity in cancer. Nature Reviews Cancer. 2021;21(6):345-59. https://doi.org/10.1038/s41568-021-00347-z
6. Afzal M, Sharma A, Sah AK, Chahal A. Structural and functional alterations in hematological parameters among individuals at clinically high risk for acute lymphocytic leukemia. Iraqi Journal of Hematology. 2024;13(2):159-69. https://doi.org/10.4103/ijh.ijh_61_24
7. Malard F, Mohty M. Acute lymphoblastic leukemia. The Lancet. 2020;395(10230):1146-62. https://www.sciencedirect.com/science/article/am/pii/S0140673619330181
8. Rodríguez-Malave NI. The Role of Long Non-coding RNAs in B-acute Lymphoblastic Leukemia: University of California, Los Angeles; 2015. https://escholarship.org/content/qt7vb1n706/qt7vb1n706.pdf
9. Nickerson JA, Momen-Heravi F. Long non-coding RNAs: roles in cellular stress responses and epigenetic mechanisms regulating chromatin. Nucleus. 2024;15(1):2350180. https://doi.org/10.1080/19491034.2024.2350180
10. Vasiou E. The role of long non-coding RNAs in male infertility: ARISTOTLE UNIVERSITY OF THESSALONIKI; 2024. https://ikee.lib.auth.gr/record/359909/files/GRI-2024-46641.pdf
11. Statello L, Guo C-J, Chen L-L, Huarte M. Gene regulation by long non-coding RNAs and their biological functions. Nature reviews Molecular cell biology. 2021;22(2):96-118. https://doi.org/10.1038/s41580-020-00315-9
12. Mattick JS, Amaral PP, Carninci P, Carpenter S, Chang HY, Chen L-L, et al. Long non-coding RNAs: definitions, functions, challenges and recommendations. Nature reviews Molecular cell biology. 2023;24(6):430-47. https://doi.org/10.1038/s41580-022-00566-8
13. Qi P, Du X. The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Modern Pathology. 2013;26(2):155-65. https://doi.org/10.1038/modpathol.2012.160
14. Yazdi N, Houshmand M, Atashi A, Kazemi A, Najmedini AA, Zarif MN. Long noncoding RNA PVT1: potential oncogene in the development of acute lymphoblastic leukemia. Turkish Journal of Biology. 2018;42(5):405-13. https://doi.org/10.3906/biy-1801-46
15. Liguori G, Cerrone M, De Chiara A, Tafuto S, de Bellis MT, Botti G, et al. The role of lncRNAs in rare tumors with a focus on Hox transcript antisense RNA (HOTAIR). International Journal of Molecular Sciences. 2021;22(18):10160. https://doi.org/10.3390/ijms221810160
16. Cantile M, Di Bonito M, Cerrone M, Collina F, De Laurentiis M, Botti G. Long non-coding RNA HOTAIR in breast cancer therapy. Cancers. 2020;12(5):1197. https://doi.org/10.3390/cancers12051197
17. Chen L, Qian X, Wang Z, Zhou X. The HOTAIR lncRNA: A remarkable oncogenic promoter in human cancer metastasis. Oncology Letters. 2021;21(4):302. https://doi.org/10.3892/ol.2021.12563
18. Amirinejad R, Rezaei M, Shirvani-Farsani Z. An update on long intergenic noncoding RNA p21: a regulatory molecule with various significant functions in cancer. Cell & Bioscience. 2020;10(1):82. https://doi.org/10.1186/s13578-020-00445-9
19. Mousavi Z, Ghorbian S, Rezamand A, Roshangar L, Jafari B. Expression profile of LncRNAs in childhood acute lymphoblastic leukemia: A pilot study. Pharmaceutical Sciences. 2020;27(3):385-92. https://doi.org/10.34172/PS.2020.84
20. Norouzi A, Motaghi M, Hassanshahi G, Nazari-Robati M. Exploring the expression profile of vitamin D receptor and its related long non-coding RNAs in patients with acute lymphoblastic leukemia. Revista da Associação Médica Brasileira. 2021;67(8):1113-7. https://doi.org/10.1590/1806-9282.20210451
21. Bhojwani D, Yang JJ, Pui C-H. Biology of childhood acute lymphoblastic leukemia. Pediatric Clinics of North America. 2015;62(1):47. https://doi.org/10.1016/j.pcl.2014.09.004
22. Al Gwaiz LA, Bassioni W. Immunophenotyping of acute lymphoblastic leukemia using immunohistochemistry in bone marrow biopsy specimens. Histology and Histopathology. 2008. https://doi.org/10.14670/hh-23.1223
23. Tian T, Wang M, Lin S, Guo Y, Dai Z, Liu K, et al. The impact of lncRNA dysregulation on clinicopathology and survival of breast cancer: a systematic review and meta-analysis. Molecular therapy Nucleic acids. 2018;12:359-69. https://doi.org/10.1016/j.omtn.2018.05.018
24. Mitobe Y, Takayama K-i, Horie-Inoue K, Inoue S. Prostate cancer-associated lncRNAs. Cancer Letters. 2018;418:159-66. https://doi.org/10.1016/j.canlet.2018.01.012
25. Izadirad M, Huang Z, Jafari F, Hamidieh AA, Gharehbaghian A, Li YD, et al. Extracellular Vesicles in Acute Leukemia: A Mesmerizing Journey With a Focus on Transferred microRNAs. Front Cell Dev Biol. 2021;9:766371. https://doi.org/10.3389/fcell.2021.766371
26. Peng W-X, Koirala P, Mo Y-Y. LncRNA-mediated regulation of cell signaling in cancer. Oncogene. 2017;36(41):5661-7. https://doi.org/10.1038/onc.2017.184
27. Ali EN, Hussein RH, Mohammed ST, Ajah HA. Effect of Vitamin D deficiency and some hematological parameters in Iraqi female patients with Systemic Lupus Erythematosus. Tikrit Journal of Pure Science. 2024;29:4. https://doi.org/10.25130/tjps.v29i4.1659
28. Tripathi A, Chuda R. Laboratory Evaluation of Acute Leukemia. StatPearls. 2025. https://www.ncbi.nlm.nih.gov/books/NBK611988/
29. Moreno CS, editor. SOX4: The unappreciated oncogene. Seminars in Cancer Biology; 2020: Elsevier. https://doi.org/10.1016/j.semcancer.2019.08.027
30. Jendrzejewski J, He H, Radomska HS, Li W, Tomsic J, Liyanarachchi S, et al. The polymorphism rs944289 predisposes to papillary thyroid carcinoma through a large intergenic noncoding RNA gene of tumor suppressor type. Proceedings of the National Academy of Sciences. 2012;109(22):8646-51. https://doi.org/10.1073/pnas.1205654109
31. Eldin RAA, Osman AA, Hassan MFAF, Ibrahim SAM, El-Sakhawy YN. HOTAIR expression and prognostic impact in acute myeloid leukemia patients. Egyptian Journal of Medical Human Genetics. 2021;22:1-11. https://doi.org/10.1080/16078454.2020.1779480
32. Zhang Y-Y, Huang S-H, Zhou H-R, Chen CJ, Tian L-H, Shen J-Z. Role of HOTAIR in the diagnosis and prognosis of acute leukemia. Oncology Reports. 2016;36(6):3113-22. https://pubmed.ncbi.nlm.nih.gov/27748863/
33. Zhu C, Wang X, Wang Y, Wang K. Functions and underlying mechanisms of lncRNA HOTAIR in cancer chemotherapy resistance. Cell Death Discovery. 2022;8(1):383. https://doi.org/10.1038/s41420-022-01174-3
34. Ouimet M, Drouin S, Lajoie M, Caron M, St-Onge P, Gioia R, et al. A childhood acute lymphoblastic leukemia-specific lncRNA implicated in prednisolone resistance, cell proliferation, and migration. Oncotarget. 2016;8(5):7477. https://doi.org/10.18632/oncotarget.13936
35. Lobo-Alves SC, de Oliveira LA, Kretzschmar GC, Valengo AE, Rosati R. Long noncoding RNA expression in acute lymphoblastic leukemia: A systematic review. Critical Reviews in Oncology/Hematology. 2024;196:104290. https://doi.org/10.1016/j.critrevonc.2024.104290
36. Almanghadim HG, Karimi B, Sanavandi M, Ghaedi K. The biological role of lncRNAs in acute lymphoblastic leukemia: An updated review. Gene. 2024;898:148074. https://doi.org/10.1016/j.gene.2023.148074
37. Hajjari M, Salavaty A. HOTAIR: an oncogenic long non-coding RNA in different cancers. Cancer biology & medicine. 2015;12(1):1-9. https://doi.org/10.7497/j.issn.2095-3941.2015.0006
38. Gao J, Wang F, Wu P, Chen Y, Jia Y. Aberrant LncRNA expression in leukemia. Journal of Cancer. 2020;11(14):4284. https://doi.org/10.7150/jca.42093
39. Sayed NH, Hammad M, Abdelrahman SA, Abdelgawad HM. Association of long non-coding RNAs and ABO blood groups with acute lymphoblastic leukemia in Egyptian children. Non-coding RNA Research. 2024;9(2):307-17. https://doi.org/10.1016/j.ncrna.2024.01.010
40. Huang X, Huang L, Xie Q, Zhang L, Huang S, Hong M, et al. LncRNAs serve as novel biomarkers for diagnosis and prognosis of childhood ALL. Biomarker Research. 2021;9(1):45. https://doi.org/10.1186/s40364-021-00303-x
41. Buono L, Iside C, De Matteo A, Stellato P, Beneduce G, de Vera d’Aragona RP, et al. Specific lncRNA signatures discriminate childhood acute leukemias: a pilot study. Cancer Cell International. 2022;22(1):373. https://doi.org/10.1186/s12935-022-02789-3