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Altered Expression of MicroRNAs in the Bone Marrow of Multiple Myeloma Patients and their Relationship to Cytogenetic Aberrations
Current Pharmaceutical Biotechnology ( IF 2.2 ) Pub Date : 2020-10-31 , DOI: 10.2174/1389201021666200320135139
Hanaa R.M. Attia 1 , Amany H. Abdelrahman 1 , Mona Hamed Ibrahim 1 , Maha M. Eid 2 , Ola M. Eid 2 , Mohamed T. Sallam 3 , Mosaad M. El Gammal 4 , Mahmoud M. Kamel 5
Affiliation  

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.



中文翻译:

多发性骨髓瘤患者骨髓中microRNA的表达变化及其与细胞遗传学异常的关系

背景:多发性骨髓瘤(MM)是一种复杂的血液系统恶性肿瘤,由多种遗传和表观遗传学改变驱动。在过去十年中,作为生物标志物的MiRNA已成为一个快速增长的研究领域。

目的:目的是研究选定的miRNA的表达模式,并探讨细胞遗传异常对MM患者治疗工具的影响。

患者和方法:选择40名埃及有症状的新诊断为MM疾病的成年患者。收集骨髓样品以研究十二种miRNA,这些miRNA是根据它们与最常见的细胞遗传学异常的关系来选择的,并具有相关的预后价值。使用实时PCR技术确定所选miRNA的相对表达。进行了荧光原位杂交(FISH)技术进行细胞遗传学分析。

结果:八个miRNA下调[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)]。四个miRNA上调[miR99b-5p(p = 0.028),miR125a-3p(p = 0.004), let7b-5p(p <0.001),let7c-5p(p <0.001)]。使用14q32.33位点的分离重排探针,阳性14q32重排与miR15a的较低表达水平之间存在显着相关性(p = 0.014) ),214-3p(p = 0.046),99b-5p(p = 0.014),146a-5p(p = 0.041)。miR30e-5p的较高表达水平与14q32阳性重排显着相关。

结论:鉴定出失控的miRNA,并确定了与14q32重排和MM发病机制的关系。

更新日期:2020-12-01
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