Department of Biomedical and Dental Sciences and Morphofunctional Images, Policlinico Universitario, University of Messina, 98125, Messina, Italy.
Department of Biomedical and Dental Sciences and Morphofunctional Images, Policlinico Universitario, University of Messina, 98125, Messina, Italy.
Pathol Res Pract. 2021 Feb;218:153317. doi: 10.1016/j.prp.2020.153317. Epub 2020 Dec 13.
Monoclonal gammopathy of undetermined significance (MGUS) is a pre-malignant abnormality of plasma cells, with increased serum levels of immunoglobulins. Patients with MGUS may evolve to multiple myeloma through a multistep process including deregulated gene expression. microRNAs are small non-coding RNA molecules involved in post-transcriptional regulation of crucial biological processes, such as morphogenesis, cell differentiation, apoptosis, and cancer. This study aimed to evaluate microRNA expression on peripheral lymph-monocytes from MGUS subjects compared with healthy controls using qPCR arrays. Blood samples were collected by venipuncture from fifteen, newly diagnosed MGUS patients and fifteen healthy subjects. A further group (validation group) of six newly diagnosed MGUS patients and five healthy control were enrolled for the validation of miRNAs and their mRNAs target. The study was conducted performing miProfile miRNA qPCR arrays, followed by validation of miRNAs and related mRNA targets through RT-qPCR. The functional interaction between microRNAs and target gene were obtained by Ingenuity Pathways Analysis (IPA). IPA network analysis identified only molecules and relationships experimentally observed in peripheral lymphomonocytes. The following miRNAs :133a-3p, 16-5p, 291-3p, 23a-3p, 205-5p, 17-5p, 7a-5p, 221-3p, 30c-5p, 126a-3p,155-5p, let-7a-5p and 26a-5p, involved in the regulation of genes with a role in lymphocyte homeostasis, cell proliferation, apoptosis, and multiple myeloma (MM) progression, were differently expressed in MGUS with respect to healthy subjects. This miRNA signature and its relative targets could be considered for the formulation of new therapeutic strategies in the prophylaxis or treatment of monoclonal gammopathies.
意义未明的单克隆丙种球蛋白血症(MGUS)是一种浆细胞的恶性前异常,伴有血清免疫球蛋白水平升高。MGUS 患者可能通过包括基因表达失调在内的多步过程进展为多发性骨髓瘤。microRNA 是参与形态发生、细胞分化、细胞凋亡和癌症等关键生物学过程的转录后调控的小非编码 RNA 分子。本研究旨在使用 qPCR 阵列评估 MGUS 患者与健康对照者外周血淋巴细胞中的 microRNA 表达。通过静脉穿刺从 15 例新诊断的 MGUS 患者和 15 例健康对照者中采集血样。另外招募了 6 例新诊断的 MGUS 患者和 5 例健康对照者作为验证 microRNA 及其靶 mRNA 的验证组。进行了 miProfile microRNA qPCR 阵列分析,随后通过 RT-qPCR 验证 microRNA 和相关的靶 mRNA 靶标。通过 Ingenuity Pathways Analysis(IPA)获得 microRNA 与靶基因之间的功能相互作用。IPA 网络分析仅确定了在周围淋巴单核细胞中通过实验观察到的分子和关系。以下 microRNA:133a-3p、16-5p、291-3p、23a-3p、205-5p、17-5p、7a-5p、221-3p、30c-5p、126a-3p、155-5p、let-7a-5p 和 26a-5p,参与调节与淋巴细胞稳态、细胞增殖、凋亡和多发性骨髓瘤(MM)进展相关的基因,在 MGUS 患者中的表达与健康对照者不同。该 microRNA 特征及其相对靶标可用于制定新的治疗策略,以预防或治疗单克隆丙种球蛋白病。