PMID- 26717976 OWN - NLM STAT- MEDLINE DCOM- 20161028 LR - 20191210 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 35 IP - 3 DP - 2016 Mar TI - Expression and regulation of COP1 in chronic lymphocytic leukemia cells for promotion of cell proliferation and tumorigenicity. PG - 1493-500 LID - 10.3892/or.2015.4526 [doi] AB - 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. FAU - Fu, Chunling AU - Fu C AD - Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China. FAU - Gong, Yanqing AU - Gong Y AD - Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China. FAU - Shi, Xuanxuan AU - Shi X AD - Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China. FAU - Shi, Hengliang AU - Shi H AD - Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China. FAU - Wan, Yan AU - Wan Y AD - Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China. FAU - Wu, Qingyun AU - Wu Q AD - Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China. FAU - Xu, Kailin AU - Xu K AD - Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151228 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (FOXO1 protein, human) RN - 0 (Forkhead Box Protein O1) RN - 0 (Forkhead Transcription Factors) RN - EC 2.3.2.27 (COP1 protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase) RN - EC 2.7.11.1 (p21-Activated Kinases) SB - IM MH - Animals MH - Apoptosis/genetics MH - Carcinogenesis/*genetics MH - Cell Cycle Checkpoints/genetics MH - Cell Proliferation/*genetics MH - Chromosome Aberrations MH - Female MH - Forkhead Box Protein O1 MH - Forkhead Transcription Factors/genetics MH - Gene Expression Regulation, Leukemic/genetics MH - Humans MH - Leukemia, Lymphocytic, Chronic, B-Cell/*genetics/pathology MH - Leukocytes, Mononuclear/metabolism/pathology MH - Male MH - Mice MH - Ubiquitin-Protein Ligases/*biosynthesis/genetics MH - Xenograft Model Antitumor Assays MH - ZAP-70 Protein-Tyrosine Kinase/biosynthesis/genetics MH - p21-Activated Kinases/genetics EDAT- 2016/01/01 06:00 MHDA- 2016/11/01 06:00 CRDT- 2016/01/01 06:00 PHST- 2015/10/11 00:00 [received] PHST- 2015/11/18 00:00 [accepted] PHST- 2016/01/01 06:00 [entrez] PHST- 2016/01/01 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] AID - 10.3892/or.2015.4526 [doi] PST - ppublish SO - Oncol Rep. 2016 Mar;35(3):1493-500. doi: 10.3892/or.2015.4526. Epub 2015 Dec 28.