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骨髓间充质基质细胞衍生的细胞外囊泡微小RNA-101在骨髓增生异常综合征中随疾病进展而下调。

Downregulation of extracellular vesicle microRNA-101 derived from bone marrow mesenchymal stromal cells in myelodysplastic syndrome with disease progression.

作者信息

Saitoh Yuu, Umezu Tomohiro, Imanishi Satoshi, Asano Michiyo, Yoshizawa Seiichiro, Katagiri Seiichiro, Suguro Tamiko, Fujimoto Hiroaki, Akahane Daigo, Kobayashi-Kawana Chiaki, Ohyashiki Junko H, Ohyashiki Kazuma

机构信息

Department of Hematology, Tokyo Medical University, Tokyo 160-8402, Japan.

Department of Hematology, Shizuoka General Hospital, Shizuoka 420-8527, Japan.

出版信息

Oncol Lett. 2020 Mar;19(3):2053-2061. doi: 10.3892/ol.2020.11282. Epub 2020 Jan 9.

Abstract

To evaluate the mechanism underlying the communication between myeloid malignant and bone marrow (BM) microenvironment cells in disease progression, the current study established BM mesenchymal stromal cells (MSCs) and assessed extracellular vesicle (EV) microRNA (miR) expression in 22 patients with myelodysplastic syndrome (MDS) and 7 patients with acute myeloid leukemia and myelodysplasia-related changes (AML/MRC). Patients with MDS were separated into two categories based on the revised International Prognostic Scoring System (IPSS-R), and EV-miR expression in BM-MSCs was evaluated using a TaqMan low-density array. The selected miRs were evaluated using reverse transcription-quantitative PCR. The current study demonstrated that the expression of BM-MSC-derived EV-miR was heterogenous and based on MDS severity, the expression of EV-miR-101 was lower in high-risk group and patients with AML/MRC compared with the control and low-risk groups. This reversibly correlated with BM blast percentage, with which the cellular miR-101 from BM-MSCs or serum EV-miR-101 expression exhibited no association. Database analyses indicated that miR-101 negatively regulated cell proliferation and epigenetic gene expression. The downregulation of BM-MSC-derived EV-miR-101 may be associated with cell-to-cell communication and may accelerate the malignant process in MDS cells.

摘要

为了评估骨髓恶性细胞与骨髓(BM)微环境细胞在疾病进展过程中相互作用的潜在机制,本研究建立了BM间充质基质细胞(MSCs),并评估了22例骨髓增生异常综合征(MDS)患者和7例急性髓系白血病伴骨髓增生异常相关改变(AML/MRC)患者的细胞外囊泡(EV)微小RNA(miR)表达情况。根据修订的国际预后评分系统(IPSS-R)将MDS患者分为两类,并使用TaqMan低密度阵列评估BM-MSCs中EV-miR的表达。使用逆转录定量PCR评估所选的miR。本研究表明,BM-MSC来源的EV-miR表达具有异质性,基于MDS的严重程度,与对照组和低风险组相比,高风险组和AML/MRC患者中EV-miR-101的表达较低。这与BM原始细胞百分比呈可逆相关,而BM-MSCs中的细胞miR-101或血清EV-miR-101表达与之无关联。数据库分析表明,miR-101负向调节细胞增殖和表观遗传基因表达。BM-MSC来源的EV-miR-101的下调可能与细胞间通讯有关,并可能加速MDS细胞的恶性进程。

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