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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

General Research Article

Altered Expression of MicroRNAs in the Bone Marrow of Multiple Myeloma Patients and their Relationship to Cytogenetic Aberrations

Author(s): Hanaa R.M. Attia*, Amany H. Abdelrahman, Mona H. Ibrahim, Maha M. Eid, Ola M. Eid, Mohamed T. Sallam, Mosaad M. El Gammal and Mahmoud M. Kamel

Volume 21, Issue 13, 2020

Page: [1394 - 1401] Pages: 8

DOI: 10.2174/1389201021666200320135139

Price: $65

Abstract

Background: Multiple Myeloma (MM) is a complex hematologic malignancy, driven by several genetic and epigenetic alterations. MiRNAs as biomarkers have become a rapidly growing research area in the last decade.

Aim: The aim was to study the expression pattern of selected miRNAs and to explore the impact of cytogenetic aberrations in MM patients for therapeutic tools.

Patients and Methods: Forty Egyptian adult patients were selected for the study with symptomatic newly diagnosed MM disease. Bone marrow samples were collected to investigate twelve miRNAs selected according to their relation to the most common cytogenetic aberrations with relevant prognostic value. The relative expression of the selected miRNAs was determined using a real-time PCR technique. Fluorescence In Situ Hybridization (FISH) technique was performed for cytogenetic analysis.

Results: Eight miRNAs were down-regulated [miR-15a (p<0.001), miR214-3p (p<0.001), miR135b (p<0.001), miR19a-3p (p<0.001), miR19b-3p ((p=0.026), miR30e-5p (NS), miR133a (NS), miR146a- 5p (p<0.001)]. Four miRNAs were up-regulated [miR99b-5p (p=0.028), miR125a-3p (p=0.004), let7b- 5p (p<0.001), let7c-5p (p<0.001)]. Significant relation was observed between positive 14q32 rearrangement using the break apart re-arrangement probe for 14q32.33 locus and lower expression levels of miR15a (p= 0.014), 214-3p (p=0.046), 99b-5p (p=0.014), 146a-5p (p=0.041). A higher expression level of miR30e-5p was significantly related to positive 14q32 rearrangement.

Conclusion: Deregulated miRNAs were identified and the association with 14q32 rearrangement and MM pathogenesis has been determined.

Keywords: Multiple myeloma, cytogenetics, prognostic markers, microRNAs, B-cell malignancy, FISH.

Graphical Abstract

[1]
Becker, N. Epidemiology of multiple myeloma. Recent Results Cancer Res., 2011, 183, 25-35.
[http://dx.doi.org/10.1007/978-3-540-85772-3_2] [PMID: 21509679]
[2]
Howlader, N.; Noone, A.M.; Yu, M.; Cronin, K.A. Use of imputed population-based cancer registry data as a method of accounting for missing information: Application to estrogen receptor status for breast cancer. Am. J. Epidemiol., 2012, 176(4), 347-356.
[http://dx.doi.org/10.1093/aje/kwr512] [PMID: 22842721]
[3]
El Husseiny, N.M.; Kasem, N.; El Azeeim, H.A.; Mattar, M.W. Multiple myeloma: A descriptive study of 217 Egyptian patients. Ann. Hematol., 2014, 93(1), 141-145.
[http://dx.doi.org/10.1007/s00277-013-1849-3] [PMID: 23892925]
[4]
Fonseca, R.; Monge, J.; Dimopoulos, M.A. Staging and prognostication of multiple myeloma. Expert Rev. Hematol., 2014, 7(1), 21-31.
[http://dx.doi.org/10.1586/17474086.2014.882224] [PMID: 24483346]
[5]
Prideaux, S.M.; Conway O’Brien, E.; Chevassut, T.J. The RAG Model: A new paradigm for genetic risk stratification in multiple myeloma. Bone Marrow Res., 2014, 2014, 526-568.
[http://dx.doi.org/10.1155/2014/526568] [PMID: 25295194]
[6]
Ciolli, S. Multiple myeloma. Clin. Cases Miner. Bone Metab., 2012, 9(3), 150-152.
[PMID: 23289028]
[7]
Segges, P.; Braggio, E.; Minnicelli, C.; Hassan, R.; Zalcberg, I.R.; Maiolino, A. Genetic aberrations in multiple myeloma characterized by cIg-FISH: A Brazilian context. Braz. J. Med. Biol. Res., 2016, 49(5)e5034
[http://dx.doi.org/10.1590/1414-431x20155034] [PMID: 27074166]
[8]
Hu, Y.; Chen, W.; Chen, S.; Huang, Z. Cytogenetic abnormality in patients with multiple myeloma analyzed by fluorescent In Situ hybridization. OncoTargets Ther., 2016, 9, 1145-1149.
[http://dx.doi.org/10.2147/OTT.S95818] [PMID: 27042105]
[9]
Amodio, N.; Di Martino, M.T.; Neri, A.; Tagliaferri, P.; Tassone, P. Non-coding RNA: A novel opportunity for the personalized treatment of multiple myeloma. Expert Opin. Biol. Ther., 2013, 13(Suppl. 1), S125-S137.
[http://dx.doi.org/10.1517/14712598.2013.796356] [PMID: 23692413]
[10]
Benetatos, L.; Vartholomatos, G. Deregulated microRNAs in multiple myeloma. Cancer, 2012, 118(4), 878-887.
[http://dx.doi.org/10.1002/cncr.26297] [PMID: 21837684]
[11]
Gutiérrez, N.C.; Sarasquete, M.E.; Misiewicz-Krzeminska, I.; Delgado, M.; De Las Rivas, J.; Ticona, F.V.; Fermiñán, E.; Martín-Jiménez, P.; Chillón, C.; Risueño, A.; Hernández, J.M.; García-Sanz, R.; González, M.; San Miguel, J.F. Deregulation of microRNA expression in the different genetic subtypes of multiple myeloma and correlation with gene expression profiling. Leukemia, 2010, 24(3), 629-637.
[http://dx.doi.org/10.1038/leu.2009.274] [PMID: 20054351]
[12]
Criteria for the Diagnosis of Multiple Myeloma. October 29. Diagnosis; Staging & Monitoring, 2015.
[13]
Pinkel, D.; Straumer, T.; Gray, I. Cytogenetic analysis using quantitative, high sensitivity: Fluorescence In Situ hybridization. Proc. Natl. Acad. Sci. USA, 1986, 83, 2934-2938.
[14]
Bergsagel, P.L.; Mateos, M.N.C.; Rajkumar, S.V.; Jesús, F.; San Miguel, J. Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma. Blood, 2013, 121, 884-892.
[15]
Saki, N.; Abroun, S.; Hajizamani, S.; Rahim, F.; Shahjahani, M. Association of chromosomal translocation and MiRNA expression with the pathogenesis of multiple myeloma. Cell J., 2014, 16(2), 99-110.
[PMID: 24567933]
[16]
Chan, Y.H. Biostatistics 102: Quantitative data--parametric & non-parametric tests. Singapore Med. J., 2003, 44(8), 391-396.
[PMID: 14700417]
[17]
Chan, Y.H. Biostatistics 104: Correlational analysis. Singapore Med. J., 2003, 44(12), 614-619.
[PMID: 14770254]
[18]
Hao, M.; Zhang, L.; An, G.; Sui, W.; Yu, Z.; Zou, D.; Xu, Y.; Chang, H.; Qiu, L. Suppressing miRNA-15a/-16 expression by interleukin-6 enhances drug-resistance in myeloma cells. J. Hematol. Oncol., 2011, 4, 37.
[http://dx.doi.org/10.1186/1756-8722-4-37] [PMID: 21936961]
[19]
Zhang, L.; Zhou, L.; Shi, M.; Kuang, Y.; Fang, L. Downregulation of miRNA-15a and miRNA-16 promote tumor proliferation in multiple myeloma by increasing CABIN1 expression. Oncol. Lett., 2018, 15(1), 1287-1296.
[PMID: 29399181]
[20]
Misiewicz-Krzeminska, I.; Sarasquete, M.E.; Quwaider, D.; Krzeminski, P.; Ticona, F.V.; Paíno, T.; Delgado, M.; Aires, A.; Ocio, E.M.; García-Sanz, R.; San Miguel, J.F.; Gutiérrez, N.C. Restoration of microRNA-214 expression reduces growth of myeloma cells through positive regulation of P53 and inhibition of DNA replication. Haematologica, 2013, 98(4), 640-648.
[http://dx.doi.org/10.3324/haematol.2012.070011] [PMID: 23100276]
[21]
Hao, M.; Zang, M.; Wendlandt, E.; Xu, Y.; An, G.; Gong, D.; Li, F.; Qi, F.; Zhang, Y.; Yang, Y.; Zhan, F.; Qiu, L. Low serum miR-19a expression as a novel poor prognostic indicator in multiple myeloma. Int. J. Cancer, 2015, 136(8), 1835-1844.
[http://dx.doi.org/10.1002/ijc.29199] [PMID: 25220540]
[22]
Wen, D.; Li, S.; Ji, F.; Cao, H.; Jiang, W.; Zhu, J.; Fang, X. miR-133b acts as a tumor suppressor and negatively regulates FGFR1 in gastric cancer. Tumour Biol., 2013, 34(2), 793-803.
[http://dx.doi.org/10.1007/s13277-012-0609-7] [PMID: 23296701]
[23]
Alzrigat, M.; Jernberg-Wiklund, H. The miR-125a and miR-320c are potential tumor suppressor microRNAs epigenetically silenced by the polycomb repressive complex 2 in multiple myeloma. RNA Dis., 2017, 4(2)e1529
[http://dx.doi.org/10.14800/rd.1529] [PMID: 28664185]
[24]
Wang, X.; Cao, L.; Wang, Y.; Wang, X.; Liu, N.; You, Y. Regulation of let-7 and its target oncogenes.(Review) Oncol. Lett., 2012, 3(5), 955-960.
[http://dx.doi.org/10.3892/ol.2012.609] [PMID: 22783372]

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