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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

NDRG2 mRNA levels and miR-28-5p and miR-650 activity in chronic lymphocytic leukemia

Authors: Yu-Qiong Yang, Tian Tian, Hua-Yuan Zhu, Jin-Hua Liang, Wei Wu, Jia-Zhu Wu, Yi Xia, Li Wang, Lei Fan, Jian-Yong Li, Wei Xu

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

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).

Methods

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.

Results

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.

Conclusions

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.
Appendix
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Metadata
Title
NDRG2 mRNA levels and miR-28-5p and miR-650 activity in chronic lymphocytic leukemia
Authors
Yu-Qiong Yang
Tian Tian
Hua-Yuan Zhu
Jin-Hua Liang
Wei Wu
Jia-Zhu Wu
Yi Xia
Li Wang
Lei Fan
Jian-Yong Li
Wei Xu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4915-3

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