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Namazi, F., Hadi, N., Moghimi, M., Eshaghiyan, A., & Nateghi, B. (2019). Down-regulation of miR-193b-3p and miR-376a-3p in Chronic Lymphocytic Leukemia. Research in Molecular Medicine (RMM), 6(3). https://doi.org/10.18502/rmm.v6i3.4609
https://doi.org/10.18502/rmm.v6i3.4609
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Faezeh Namazi
Faezeh Namazi
Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran
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Nasrin Hadi
Nasrin Hadi
Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran
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Mansour Moghimi
Mansour Moghimi
Department of Pathology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Amir Eshaghiyan
Amir Eshaghiyan
Department of Genetics, Arsanjan Branch, Islamic Azad University, Arsanjan, Shiraz, Iran
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Behnaz Nateghi
Behnaz Nateghi
Department of Biochemistry, Faculty of Science, Nourdanesh Institutions of Higher Education, Meimeh, Isfahan, Iran
Published Date
- Jun 19, 2019
Down-regulation of miR-193b-3p and miR-376a-3p in Chronic Lymphocytic Leukemia
Abstract
Background: Chronic lymphocytic leukemia (CLL) is the most common adult human leukemia. Studies revealed that microRNAs (miRNAs) can function as oncogenes or tumor suppressors in CLL and that the expression of miRNAs, such as miR-193b-3p and miR-376a-3p change in several diseases. We aimed to elucidate the changes in miR- 193b-3p and miR-376a-3p expression in CLL and determine their potential as diagnostic biomarkers for this disease.
Materials and Methods: We investigated miR-193b-3p and miR-376a-3p expression by quantitative real-time PCR in peripheral blood mononuclear cells of 30 patients with CLL and 30 healthy individuals. Moreover, in silico molecular enrichment analysis was conducted on predicted and validated targets of miR-193b-3p and miR-376a-3p from the miRecords and miRTarBase databases.
Results: The expression of miR-193b-3p and miR-376a-3p was significantly different between the two groups (P<0.0001 and P < 0.0001, respectively).
Conclusion: Based on these findings, miR-193b-3p and miR-376a-3p could be novel biomarkers for the early diagnosis of CLL and could be used to design new CLL control strategies.
References
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[15] Li H, Xu Y, Qiu W, Zhao D, Zhang Y. Tissue miR-193b as a novel biomarker for patients with ovarian cancer. Med Sci Monit. 2015;21:3929.
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[18] Zheng Y, Yin L, Chen H, Yang S, Pan C, Lu S, et al. miR-376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma. FEBS Lett. 2012;586(16):2396- 403.
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[21] Xiao F, Zuo Z, Cai G, Kang S, Gao X, Li T. miRecords: an integrated resource for microRNA–target interactions. Nucleic Acids Res. 2008;37(suppl.1): D105-10.
[22] Hsu SD, Lin FM, Wu WY, Liang C, Huang WC, Chan WL, et al. miRTarBase: a database curates experimentally validated microRNA–target interactions. Nucleic Acids Res. 2010;39(suppl.1): D163-9.
[23] Fathullahzadeh S, Mirzaei H, Honardoost MA, Sahebkar A, Salehi M. Circulating microRNA-192 as a diagnostic biomarker in human chronic lymphocytic leukemia. Cancer Gene Ther. 2016;23(10):32-37.
[24] Moussay E, Wang K, Cho JH, van Moer K, Pierson S, Paggetti J, Nazarov PV, Palissot V, Hood LE, Berchem G, Galas DJ. MicroRNA as biomarkers and regulators in B-cell chronic lymphocytic leukemia. Proc Natl Acad Sci. 2011;108(16):6573-8.
[25] Filip AA, Grenda A, Popek S, Koczkodaj D, Michalak-Wojnowska M, Budzyński M, Wąsik-Szczepanek E, Zmorzyński S, Karczmarczyk A, Giannopoulos K. Expression of circulating miRNAs associated with lymphocyte differentiation and activation in CLL—another piece in the puzzle. Ann Hematol. 2017;96(1):33-50.
[26] Wu K, Zhao Z, Ma J, Chen J, Peng J, Yang S, He Y. Deregulation of miR-193b affects the growth of colon cancer cells via transforming growth factor-β and regulation of the SMAD3 pathway. Oncol Lett. 2017;13(4):2557-62.
[27] Witkowska M, Majchrzak A, Cebula-Obrzut B, Wawrzyniak E, Robak T, Smolewski P. The distribution and potential prognostic value of SMAD protein expression in chronic lymphocytic leukemia. Tumor Biol. 2017;39(3):1010428317694551.
[28] Zhang H, Jiang X, Zhang Y, Xu B, Hua J, Ma T, Zheng W, Sun R, Shen W, Cooke HJ, Hao Q. microRNA 376a regulates follicle assembly by targeting Pcna in fetal and neonatal mouse ovaries. Reproduction. 2014;148(1):43-54.
[29] Giglio AD, O’brien S, Ford RJ, Manning J, Saya H, Keating M, Johnston D, Chamone DF, Deisseroth AB. Proliferating cell nuclear antigen (PCNA) expression in chronic lymphocytic leukemia (CLL). Leukemia Lymphoma. 1993;10(4-5):265-71.
[2] Bueso-Ramos CE, Ferrajoli A, Medeiros LJ, Keating MJ, Estrov Z. Aberrant morphology, proliferation, and apoptosis of B-cell chronic lymphocytic leukemia cells. Hematology. 2004; 9:279-86.
[3] Chiorazzi N. Cell proliferation and death: forgotten features of chronic lymphocytic leukemia B cells. Best Pract Res Clin Haematol. 2007;20:399-413.10.1016/j.beha.2007.03.007.
[4] DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS and Jemal A. Cancer treatment and survivorship statistics. CA Cancer J Clin. 2014; 64:252-71.
[5] Sgambati M, Linet M, Devesa S. Chronic lymphocytic leukemia, epidemiological, familial, and genetic aspects. Chronic lymphocytic leukemias, Revised and Expanded, 2nd edn. In: Cheson B, (ed). Marcel Dekker, Inc: New York, NY, USA, 2001 pp 33–62.
[6] Mirzaei H, Fathullahzadeh S, Khanmohammadi R, Darijani M, Momeni F, Masoudifar A, et al. State of the art in microRNA as diagnostic and therapeutic biomarkers in chronic lymphocytic leukemia. J Cell Physiol. 2018; 233(2):888-900.
[7] Fernando TR, Rodriguez-Malave NI and Rao DS. MicroRNAs in B cell development and malignancy. J Hematol Oncol. 2012;5:7.
[8] Martini V, Frezzato F, Severin F, Raggi F, Trimarco V, Martinello L, Molfetta R, Visentin A, Facco M, Semenzato G, Paolini R. Abnormal regulation of BCR signalling by c-Cbl in chronic lymphocytic leukaemia. Oncotarget. 2018;9 :32219-31.
[9] Hershkovitz-Rokah O, Geva P, Salmon-Divon M, Shpilberg O, Liberman-Aronov S. Network analysis of microRNAs, genes and their regulation in diffuse and follicular B-cell lymphomas. Oncotarget. 2018; 9(8):28-79.
[10] Reddy KB. MicroRNA (miRNA) in cancer. Cancer Cell Int. 2015;15:38-42.
[11] Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99(24):15524-9.
[12] Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141(5):672-5.
[13] Mets E, Van der Meulen J, Van Peer G, Boice M, Mestdagh P, Van de Walle I, et al. MicroRNA-193b-3p acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia. Leukemia. 2015;29(4):79-86.
[14] Rauhala HE, Jalava SE, Isotalo J, Bracken H, Lehmusvaara S, Tammela TL, et al. miR193b is an epigenetically regulated putative tumor suppressor in prostate cancer. Int J Cancer. 2010;127(6):1363-72.
[15] Li H, Xu Y, Qiu W, Zhao D, Zhang Y. Tissue miR-193b as a novel biomarker for patients with ovarian cancer. Med Sci Monit. 2015;21:3929.
[16] Herr I, Sähr H, Zhao Z, Yin L, Omlor G, Lehner B, Fellenberg J. MiR-127 and miR-376a act as tumor suppressors by in vivo targeting of COA1 and PDIA6 in giant cell tumor of bone. Cancer Lett. 2017;409:49-55.
[17] Meng X, Joosse SA, Müller V, Trillsch F, Milde-Langosch K, Mahner S, et al. Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients. Br J Cancer. 2015;113(9):1358.
[18] Zheng Y, Yin L, Chen H, Yang S, Pan C, Lu S, et al. miR-376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma. FEBS Lett. 2012;586(16):2396- 403.
[19] Negrini M, Cutrona G, Bassi C, Fabris S, Zagatti B, Colombo M, et al. microRNAome expression in chronic lymphocytic leukemia: comparison with normal B-cell subsets and correlations with prognostic and clinical parameters. Clin Cancer Res.2014;10:723.
[20] Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C T method. Nat Protoc. 2008;3(6):1101.
[21] Xiao F, Zuo Z, Cai G, Kang S, Gao X, Li T. miRecords: an integrated resource for microRNA–target interactions. Nucleic Acids Res. 2008;37(suppl.1): D105-10.
[22] Hsu SD, Lin FM, Wu WY, Liang C, Huang WC, Chan WL, et al. miRTarBase: a database curates experimentally validated microRNA–target interactions. Nucleic Acids Res. 2010;39(suppl.1): D163-9.
[23] Fathullahzadeh S, Mirzaei H, Honardoost MA, Sahebkar A, Salehi M. Circulating microRNA-192 as a diagnostic biomarker in human chronic lymphocytic leukemia. Cancer Gene Ther. 2016;23(10):32-37.
[24] Moussay E, Wang K, Cho JH, van Moer K, Pierson S, Paggetti J, Nazarov PV, Palissot V, Hood LE, Berchem G, Galas DJ. MicroRNA as biomarkers and regulators in B-cell chronic lymphocytic leukemia. Proc Natl Acad Sci. 2011;108(16):6573-8.
[25] Filip AA, Grenda A, Popek S, Koczkodaj D, Michalak-Wojnowska M, Budzyński M, Wąsik-Szczepanek E, Zmorzyński S, Karczmarczyk A, Giannopoulos K. Expression of circulating miRNAs associated with lymphocyte differentiation and activation in CLL—another piece in the puzzle. Ann Hematol. 2017;96(1):33-50.
[26] Wu K, Zhao Z, Ma J, Chen J, Peng J, Yang S, He Y. Deregulation of miR-193b affects the growth of colon cancer cells via transforming growth factor-β and regulation of the SMAD3 pathway. Oncol Lett. 2017;13(4):2557-62.
[27] Witkowska M, Majchrzak A, Cebula-Obrzut B, Wawrzyniak E, Robak T, Smolewski P. The distribution and potential prognostic value of SMAD protein expression in chronic lymphocytic leukemia. Tumor Biol. 2017;39(3):1010428317694551.
[28] Zhang H, Jiang X, Zhang Y, Xu B, Hua J, Ma T, Zheng W, Sun R, Shen W, Cooke HJ, Hao Q. microRNA 376a regulates follicle assembly by targeting Pcna in fetal and neonatal mouse ovaries. Reproduction. 2014;148(1):43-54.
[29] Giglio AD, O’brien S, Ford RJ, Manning J, Saya H, Keating M, Johnston D, Chamone DF, Deisseroth AB. Proliferating cell nuclear antigen (PCNA) expression in chronic lymphocytic leukemia (CLL). Leukemia Lymphoma. 1993;10(4-5):265-71.