title: HIF-α Promotes Chronic Myelogenous Leukemia Cell Proliferation by Upregulating p21 Expression.
abstract: We sought to determine the expression levels of hypoxia-inducible factor-1α (HIF-1α) in the bone marrow chronic myelogenous leukemia (CML) patients. We also tried to determine the roles HIF-1α in the proliferation of CML cells by small interfering RNA (siRNA) knockdown. Real-time PCR was performed to determine the expression levels of HIF-1α in the bone marrows of CML patients and healthy volunteers. HIF-1α knockdown by siRNA in K562 cells was confirmed by RT-PCR. Proliferation and colony formation of the treated cells were determined by CCK8 after HIF-1α knockdown. RT-PCR and western blotting were performed to detect mRNA and protein levels of p21 and p53 in K562 cells. HIF-1α mRNA expression in the bone marrow of CML patients was significantly higher than that in the control, which was statistically significant (P < 0.05). HIF-1α knockdown dramatically reduced the proliferation of K562 cells, which was also statistically significant (P < 0.05). HIF-1α knockdown markedly reduced the colony formation ability of K562 cells, which was also statistically significant (P < 0.05). The mRNA and protein expression of p21 were significantly reduced in K562 cell after HIF-1α knockdown with affecting the mRNA and protein levels of p53. HIF-α promotes chronic CML cell proliferation by up-regulating p21 expression.
authors.affiliation: Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Hematology, People's Hospital of Wuxi City, Wuxi, Jiangsu, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Gong
authors.affiliation: Department of Hematology, People's Hospital of Wuxi City, Wuxi, Jiangsu, China.
authors.forename: Yuanqiang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China. zhangrizr@163.com.
authors.forename: Ri
authors.initials: R
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D001853:Bone Marrow / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002766:Cholecystokinin / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C410885:cholecystokinin 8; D002766:Cholecystokinin
keywords: Chronic myeloid leukemia; HIF-1α; p21; p53