Overexpression of chromodomain helicase DNA binding protein 5 (CHD5) inhibits cell proliferation and induces cell cycle arrest and apoptosis in chronic myeloid leukemia.

Background: Chromodomain helicase DNA binding protein 5 (CHD5) was reported to be a tumor suppressor and our previous work showed CHD5 was epigenetically inactivated in human chronic myeloid leukemia (CML). This study aimed to investigate the effect of its overexpression on CML tumorigenesis.

Methods: Quantitative reverse-transcriptase PCR and Western blotting analysis were used to detect the expression of CHD5 in human CML cell lines. The endogenous CHD5 expression was activated in two CML cell lines by CRISPR/dCas9-SAM system. cell function experiments were performed including proliferation, colony formation, apoptosis, autophagy, senescence and differentiation assays. Furthermore, tumorigenicity was evaluated in nude mice xenograft model.

Results: CHD5 was down-regulated in CML cell lines compare to normal bone marrow mononuclear cells (MCs). Cell proliferation after activating CHD5 was significantly inhibited. Moreover, overexpression of CHD5 induced G2/M phase arrest and apoptosis in CML cells. In a tumor xenograft mouse model, CHD5 restoration was found to sharply repress tumor growth. Compared with the control group, overexpression of CHD5 enhanced the expression of p21 and cdc2 phosphorylation, whereas decreased the protein level of Cyclin B1. Furthermore, experiments revealed that up-regulation of CHD5 activated caspase-3, while anti-apoptosis protein Bcl-2 expression was reduced in CML cells.

Conclusions: CHD5 plays a role of anti-tumorigenic effects involved in CML cell proliferation, cell cycle arrest and apoptosis.