多发性骨髓瘤患者骨髓中 microRNAs 的表达改变及其与细胞遗传学异常的关系。

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

机构信息

Department of Clinical and Chemical Pathology, National Research Centre, Cairo, Egypt.

Department of Human Cytogenetics, National Research Centre, Cairo, Egypt.

出版信息

Curr Pharm Biotechnol. 2020;21(13):1394-1401. doi: 10.2174/1389201021666200320135139.

DOI:10.2174/1389201021666200320135139

PMID:32196445

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.

摘要

背景

多发性骨髓瘤（MM）是一种复杂的血液恶性肿瘤，由多种遗传和表观遗传改变驱动。miRNA 作为生物标志物在过去十年中成为一个快速发展的研究领域。

目的

本研究旨在研究选定 miRNA 的表达模式，并探讨细胞遗传学异常对 MM 患者治疗工具的影响。

患者和方法

选择 40 名埃及成年新诊断 MM 患者进行研究。采集骨髓样本，根据与最常见细胞遗传学异常相关的相关性和相关预后价值，研究 12 种选定的 miRNA。使用实时 PCR 技术确定选定 miRNA 的相对表达。进行荧光原位杂交（FISH）技术进行细胞遗传学分析。

结果

有 8 个 miRNA 下调[miR-15a（p<0.001），miR-214-3p（p<0.001），miR-135b（p<0.001），miR-19a-3p（p<0.001），miR-19b-3p（p=0.026），miR-30e-5p（NS），miR-133a（NS），miR-146a-5p（p<0.001）]。有 4 个 miRNA 上调[miR-99b-5p（p=0.028），miR-125a-3p（p=0.004），let-7b-5p（p<0.001），let-7c-5p（p<0.001）]。使用 14q32.33 基因座的断裂重排探针检测到 14q32 阳性重排与 miR-15a（p=0.014）、214-3p（p=0.046）、99b-5p（p=0.014）、146a-5p（p=0.041）表达水平降低显著相关。miR-30e-5p 表达水平升高与 14q32 阳性重排显著相关。