title: Silencing HCCR2 expression inhibits the proliferation of leukemia cells by inducing apoptosis and promoting cell cycle arrest.
abstract: The human cervical cancer oncogene (HCCR2) has been found to be overexpressed in a variety of human malignant tumors cells, and its function is related to cell cycle progression and survival. However, the molecular mechanisms of action of HCCR2 in leukemia remain unclear. In this study, we used the RNA interference strategy to investigate the effects of HCCR2 knockdown in the K562 leukemia cell line, and to explore the potential mechanisms involved. Following transfection with small interfering RNA (siRNA) targeting HCCR2 (HCCR2-siRNA), we examined the effects of HCCR2 knockdown on cell morphology, cell proliferation, cell cycle progression and apoptosis in K562 cells. Morphological changes were evaluated by Wright-Giemsa staining. Cell cycle progression and apoptosis were measured by flow cytometry. The expression levels of genes related to the cell cycle and apoptosis were detected by quantitative RT-PCR (qRT-PCR) and western blot analysis. HCCR2 expression at the mRNA and protein level was significantly decreased following transfection with plasmids expressing HCCR2-siRNA. Silencing HCCR2 expression significantly suppressed cell proliferation, induced G1 cell cycle arrest and promoted the apoptosis of K562 cells. Additionally, we found that the expression of Bax, p53 and p21 was significantly increased, while Bcl-2 expression was significantly decreased in the HCCR2-siRNA-transfected cells. However, the expression of p27 was not affected. These results suggest that the HCCR2 gene plays an important role in the tumorigenesis of leukemia, thus making it an attractive therapeutic target for acute leukemia.
authors.affiliation: Department of Hematology, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Shu-Kai
authors.initials: SK
authors.lastname: Qiao
authors.forename: Han-Yun
authors.initials: HY
authors.lastname: Ren
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D049109:Cell Proliferation; D048430:Cell Shape / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection
chemical_list: C476732:LETMD1 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering