NDRG2 mRNA levels and miR-28-5p and miR-650 activity in chronic lymphocytic leukemia.
NDRG2 mRNA levels and miR-28-5p and miR-650 activity in chronic lymphocytic leukemia.
复制标题
慢性淋巴细胞白血病中的 NDRG2 mRNA 水平以及 miR-28-5p 和 miR-650 活性。
DOI：
10.1186/s12885-018-4915-3
复制
发表时间：
2018-10-22
期刊：
影响因子：
3.8
通讯作者：
Xu W
中科院分区：
文献类型：
--
作者：
Yang YQ;Tian T;Zhu HY;Liang JH;Wu W;Wu JZ;Xia Y;Wang L;Fan L;Li JY;Xu W
NDRG 2在许多肿瘤中被鉴定为肿瘤抑制基因，并且在细胞增殖、分化和凋亡中起作用。最近的数据表明NDRG 2的表达被TP 53上调。此外，提出的NDRG 2失活机制包括NDRG 2启动子的表观遗传沉默和microRNA（miRNA）的下调。然而，NDRG 2及其调控miRNAs在慢性淋巴细胞白血病（CLL）中的作用研究较少。通过定量实时聚合酶链反应（qRT-PCR）评估CLL受试者中NDRG 2和microRNAs的mRNA水平。进行双荧光素酶报告基因测定以确定NDRG 2相关的miRNA。通过瞬时转染在CLL细胞中建立成熟的外源性miRNA的低表达。Western blot检测NDRG 2蛋白表达水平。流式细胞仪检测CLL细胞凋亡情况。102例CLL患者B淋巴细胞NDRG 2的表达低于40例正常人（P < 0.001）。在Binet分期较晚（P = 0.001）、乳酸脱氢酶（LDH）水平较高（P = 0.036）、免疫球蛋白重链可变区（IGHV）基因未突变（P = 0.004）和p53异常（P < 0.001）的患者中，NDRG 2 mRNA水平明显降低。这种下降与治疗时间缩短（P = 0.001）和生存率降低（P < 0.001）有关。miR-28- 5 p和miR-650的高表达分别与Binet B/C分期（P = 0.044）和IGHV未突变（P = 0.011）相关，与Binet B/C分期（P = 0.013）和p53畸变（P = 0.037）相关。抑制miR-28- 5 p或miR-650可在具有生殖系TP 53的CLL细胞中诱导更多的凋亡。NDRG 2 mRNA水平可能是CLL患者的一个有用的预后变量，上调NDRG 2转录可能是无p53畸变的CLL的一种治疗方法。本文的在线版本（10.1186/s12885-018-4915-3）包含补充材料，可供授权用户使用。
NDRG2 is identified as a tumor suppressor gene in many tumors, and functions in cell proliferation, differentiation and apoptosis. Recent data indicate that NDRG2 expression is up-regulated by TP53. Moreover, proposed mechanisms of NDRG2 inactivation include epigenetic silencing of the NDRG2 promoter and down-regulation by microRNAs (miRNAs). However, few studies have ever been done on the role of NDRG2 and the NDRG2-regulating miRNAs interference in chronic lymphocytic leukemia (CLL). NDRG2 and microRNAs mRNA levels in CLL subjects were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The dual-luciferase reporter assay was performed to determine NDRG2-related miRNAs. Low expression of mature exogenous miRNAs in CLL cells was established by transient transfection. NDRG2 protein levels in CLL cells were detected by western blot. In addition, flow cytometry was conducted to examine the apoptosis of CLL cells. Lower expression of NDRG2 was found in the B-cells from 102 CLL patients compared the 40 normal subjects (P < 0.001). Patients with advanced Binet stage (P = 0.001), high lactate dehydrogenase (LDH) level (P = 0.036), un-mutated immunoglobulin heavy chain variable region gene (IGHV) (P = 0.004) and those with p53 aberrations (P < 0.001) had a markedly lower levels of NDRG2 mRNA. This decrease was associated with briefer time-to-treatment (P = 0.001) and poorer survival (P < 0.001). High expression of miR-28-5p and miR-650 was associated with Binet B/C stage (P = 0.044) and IGHV un-mutated (P = 0.011), as well as Binet B/C stage (P = 0.013) and p53 aberrations (P = 0.037), respectively. Inhibition of miR-28-5p or miR-650 could induce more apoptosis in CLL cells with germline TP53. NDRG2 mRNA levels might be a useful prognostic variable for patients of CLL and up-regulating NDRG2 transcription may be a therapy approach in CLL without p53 aberrations. The online version of this article (10.1186/s12885-018-4915-3) contains supplementary material, which is available to authorized users.