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B 细胞非霍奇金淋巴瘤中表达的 microRNA-17-92 基因簇的意义。

Significance of the microRNA‑17‑92 gene cluster expressed in B‑cell non‑Hodgkin's lymphoma.

机构信息

Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150080, P.R. China.

出版信息

Mol Med Rep. 2019 Sep;20(3):2459-2467. doi: 10.3892/mmr.2019.10448. Epub 2019 Jul 1.

Abstract

To evaluate the prognostic value of the microRNA (miR)‑17‑92 gene cluster, the expression of miR‑17‑92 in B‑cell non‑Hodgkin's lymphoma (B‑NHL) was examined. Patients with B‑NHL, who received therapy in the Department of Hematology, Harbin Medical University Cancer Hospital between January 2012 and October 2014, were enrolled in the study. The expression of the miR‑17‑92 cluster in tumor tissue samples was detected by reverse transcription‑quantitative polymerase chain reaction analysis. The overall survival (OS) and event‑free survival (EFS) times were also investigated by the Kaplan‑Meier method and comparisons between groups were estimated using a log‑rank test. Three types of lymphoid cancer cells with wild‑type (WT), knockout of miR‑17‑92 (KO), and overexpression of miR‑17‑92 (TG), were utilized to establish a tumor xenograft model, and a reactive hyperplasia lymph cell was used as a control. The tumor incubation times and weights were examined. A total of 71 patients with B‑NHL were registered. No significant correlations were identified between the expression of miR‑17‑92 and clinical factors (P>0.05). Members of the miR‑17‑92 cluster exhibited various expression in the subtypes of B‑NHL, and the difference between follicular lymphoma (FL) and germinal center B‑cell like (GBC) was most marked. The overexpression of miR‑18, miR‑19a, and miR‑92a induced a marked reduction in the OS of patients with B‑NHL, and high‑levels of miR‑19a and miR‑92a led to a decline in EFS. The overexpression of miR‑17‑92 shortened the duration of incubation required for visualization of the xenograft tumor, whereas knockout led to inhibition of tumor formation. The expression of miR‑17‑92 in FL differed significantly from that in GBC, and miR‑19a may have a crucial effect on the OS and EFS of patients with B‑NHL.

摘要

为了评估微小 RNA(miRNA)-17-92 基因簇的预后价值,研究了 B 细胞非霍奇金淋巴瘤(B-NHL)中 miR-17-92 的表达。本研究纳入了 2012 年 1 月至 2014 年 10 月在哈尔滨医科大学附属肿瘤医院血液科接受治疗的 B-NHL 患者。采用逆转录定量聚合酶链反应分析检测肿瘤组织样本中 miR-17-92 簇的表达。通过 Kaplan-Meier 法研究总生存期(OS)和无事件生存期(EFS),并采用对数秩检验比较组间差异。利用野生型(WT)、miR-17-92 敲除(KO)和 miR-17-92 过表达(TG)三种淋巴癌细胞建立肿瘤异种移植模型,以反应性增生淋巴细胞作为对照。检测肿瘤培养时间和重量。共纳入 71 例 B-NHL 患者。miR-17-92 的表达与临床因素之间无显著相关性(P>0.05)。miR-17-92 簇成员在 B-NHL 各亚型中的表达不同,滤泡性淋巴瘤(FL)和生发中心 B 细胞样(GBC)之间的差异最为显著。miR-18、miR-19a 和 miR-92a 的过表达显著降低了 B-NHL 患者的 OS,高水平的 miR-19a 和 miR-92a 导致 EFS 下降。miR-17-92 的过表达缩短了异种移植瘤可视化所需的潜伏期,而敲除则抑制了肿瘤的形成。FL 中 miR-17-92 的表达与 GBC 有显著差异,miR-19a 可能对 B-NHL 患者的 OS 和 EFS 有重要影响。

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