Transcription factor CCAAT/enhancer-binding protein alpha and critical circadian clock downstream target gene PER2 are highly deregulated in diffuse large B-cell lymphoma

Autor:	Shayan Nabavi-Nouis, Ngan B. Doan, Sigal Gery, Jonathan W. Said, Nils H. Thoennissen, Carsten Müller-Tidow, Sam Abbassi, Gabriela B. Thoennissen, Tim Sauer, H. Phillip Koeffler
Rok vydání:	2012
Předmět:	Cancer Research endocrine system Cell Survival Biopsy Circadian clock Apoptosis Biology Article immune system diseases Genes Reporter hemic and lymphatic diseases Cell Line Tumor CEBPA medicine CCAAT-Enhancer-Binding Protein-alpha Humans Cell Proliferation Regulation of gene expression Models Genetic Gene Expression Profiling Cell Cycle Hematology Period Circadian Proteins Cell cycle medicine.disease Molecular biology BCL10 Circadian Rhythm PER2 CLOCK Gene Expression Regulation Neoplastic Oncology Cancer research Lymphoma Large B-Cell Diffuse Diffuse large B-cell lymphoma
Zdroj:	Leukemialymphoma. 53(8)
ISSN:	1029-2403
Popis:	Disturbances of circadian rhythms and mammalian clock genes have been implicated in the etiologies of many chronic illnesses, including cancer. We show that transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha)-regulated PER2 activation is a potential tumor suppressor pathway in diffuse large B-cell lymphoma (DLBCL), one of the commonest types of mature B-cell lymphoma. Expression analysis of human B-cell lymphoma samples including DLBCL (n = 50), mantle cell (n = 21), follicular (n = 25) and Burkitt (n = 18) lymphoma revealed markedly down-regulated CEBPA and PER2 mRNA levels exclusively in DLBCL samples compared to control lymphatic tissue. We demonstrated direct regulation of the circadian core clock gene PER2 by C/EBPalpha in the pro-B cell line Ba/F3, and forced expression of PER2 resulted in decreased proliferation, G0/G1 cell cycle arrest and increased rates of apoptosis. Interestingly, treatment of human DLBCL cell lines with the histone deacetylase-inhibitor suberoylanilide hydroxamic acid (SAHA) significantly increased the expression of C/EBPalpha and Per2, accompanied by cell growth inhibition; in contrast, siRNA knockdown of CEBPA reduced the anti-proliferative effect of SAHA treatment. Our results show for the first time that C/EBPalpha with its associated direct core clock gene target, PER2, are highly deregulated in DLBCL, suggesting an important tumor suppressive pathway in the pathogenesis of this lymphoma entity.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::59af452db0220e4a3227a09cb089d422 https://pubmed.ncbi.nlm.nih.gov/22260161 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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