title: Expression and regulation of COP1 in chronic lymphocytic leukemia cells for promotion of cell proliferation and tumorigenicity.
abstract: Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and mainly originates from an accumulation of abnormal B cells caused by the dysregulation of cell proliferation and apoptosis. The aberration of proliferation-related gene in CLL cells induces cell arrest at G0/G1 phase, or a small section shows rapid cell growth, which further complicates the pathogenesis of CLL. The constitutively photomorphogenic 1 (COP1), as an E3 ubiquitin ligase, is involved in many biological processes in mammalian cells, but its role in chronic lymphocytic leukemia (CLL) progression remains unclear. In the present study, we analyzed the expression of COP1 in peripheral blood mononuclear cells (PBMCs) from 23 CLL patients and 3 healthy donors. The observed upregulated expression of COP1 in CLL patients was positively correlated with CLL clinical stage and ZAP-70 expression, but not del(13q14) and del(17q-). Overexpression of COP1 significantly promoted cell colony formation and proliferation, especially contributing to the accumulation of cells in S-phase by inhibition of FoxO1 and p21. Moreover, overexpression of COP1 accelerated tumorigenicity of HG3 cells and promoted xenograft growth. Therefore, the present study revealed that COP1 plays an important role in CLL cell proliferation and tumorigenicity, and may be a useful indicator of the chronic lymphocytic leukemia processes.
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Fu
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Xuanxuan
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Hengliang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D002869:Chromosome Aberrations; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis / Q000235:genetics; D054462:p21-Activated Kinases / Q000235:genetics
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C471981:COP1 protein, human; D044767:Ubiquitin-Protein Ligases; D051746:ZAP-70 Protein-Tyrosine Kinase; D054462:p21-Activated Kinases