Long non-coding RNA CRNDE suppressing cell proliferation is regulated by DNA methylation in chronic lymphocytic leukemia

2021 
Long non-coding RNA CRNDE and DNA methylation play a vital role in the occurrence and development of chronic lymphocytic leukemia (CLL). This study attempted to investigate the biological role of CRNDE methylation in CLL. The expression and methylation levels of CRNDE in CLL cell lines (MEC-1 and HG3) before or after methylation inhibitor (5-Aza-2'-deoxycytidine, 5-Aza-CdR) treatment was detected by quantitative real-time PCR or methylation-Specific PCR. The relationship among CRNDE, miR-28 and NDRG2 was verified by luciferase reporter assay. The effect of CRNDE overexpression and 5-Aza-CdR treatment on cell proliferation and apoptosis of MEC-1 and HG3 cells were assessed by CCK8 and flow cytomery. Compared with normal B lymphocytes, CRNDE was down-regulated and the methylation level of CRNDE was increased in MEC-1 and HG3 cells. Then, 5-Aza-CdR treatment caused an increase of CRNDE expression in MEC-1 and HG3 cells by demethylation. The overexpression or demethylation of CRNDE inhibited cell proliferation and promoted apoptosis in MEC-1 and HG3 cells by up-regulating CRNDE expression. Moreover, CRNDE functioned as a competing endogenous RNA to repress miR-28, which controlled its down-stream target NDRG2. CRNDE overexpression inhibited cell proliferation and promoted apoptosis via miR-28/NDRG2 axis in CLL. In conclusion, our data elaborated that CRNDE expression was regulated by DNA methylation, and the protective effect of CRNDE on CLL was attributed to the inhibition of proliferation in CLL via miR-28/NDRG2 axis. Thus, this work highlights a novel competing endogenous RNA circuitry involving key regulators of CLL.
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