ANKHD1 represses p21 (WAF1/CIP1) promoter and promotes multiple myeloma cell growth

Página do item simplificado
dc.contributor.authorDhyani, Anamika
dc.contributor.authorMachado-Neto, Joao A.
dc.contributor.authorFavaro, Patricia [UNIFESP]
dc.contributor.authorOlalla Saad, Sara T.
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:39:49Z
dc.date.available2016-01-24T14:39:49Z
dc.date.issued2015-01-01
dc.description.abstractANKHD1 (Ankyrin repeat and KH domain-containing protein 1) is highly expressed and plays an important role in the proliferation and cell cycle progression of multiple myeloma (MM) cells. ANKHD1 downregulation modulates cell cycle gene expression and upregulates p21 irrespective of the TP53 mutational status of MM cell lines. the present study was aimed to investigate the role of ANKHD1 in MM in vitro clonogenicity and in vivo tumourigenicity, as well as the role of ANKHD1 in p21 transcriptional regulation. ANKHD1 silencing in MM cells resulted in significantly low no. of colonies formed and in slow migration as compared to control cells (p < 0.05). Furthermore, in xenograft MM mice models, tumour growth was visibly suppressed in mice injected with ANKHD1 silenced cells compared to the control group. There was a significant decrease in tumour volume (p = 0.006) as well as in weight (p = 0.02) in the group injected with silenced cells compared to those of the control group. Co-immunoprecipitation and chromatin immunoprecipitation (ChIP) assays confirmed the interaction between p21 and ANKHD1. Moreover, overexpression of ANKHD1 downregulated the activity of a p21 promoter in luciferase assays. Decrease in luciferase activity suggests a direct role of ANKHD1 in p21 transcriptional regulation. in addition confocal analysis after U266 cells were treated with Leptomycin B (LMB) for 24 h showed accumulation of ANKHD1 inside the nucleus as compared to untreated cells where ANKHD1 was found to be predominantly in cytoplasm. This suggests ANKHD1 might be shuttling between cytoplasm and nucleus. in conclusion, ANKHD1 promotes MM growth by repressing p21 a potent cell cycle regulator. (C) 2014 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Estadual Campinas, Hematol & Hemotherapy Ctr, BR-13083878 Campinas, SP, Brazil
dc.description.affiliationUniv Estadual Campinas, Hemoctr, Inst Nacl Ciencia & Tecnol Sangue, Campinas, SP, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biol Sci, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biol Sci, ICAQF, Diadema, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent252-259
dc.identifierhttp://dx.doi.org/10.1016/j.ejca.2014.11.012
dc.identifier.citationEuropean Journal of Cancer. Oxford: Elsevier B.V., v. 51, n. 2, p. 252-259, 2015.
dc.identifier.doi10.1016/j.ejca.2014.11.012
dc.identifier.issn0959-8049
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/38581
dc.identifier.wosWOS:000346851200015
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofEuropean Journal of Cancer
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectANKHD1en
dc.subjectMultiple myelomaen
dc.subjectClonogenicityen
dc.subjectTumourigenicityen
dc.subjectp21 (WAF1/CIP1)en
dc.subjectTranscriptional regulationen
dc.titleANKHD1 represses p21 (WAF1/CIP1) promoter and promotes multiple myeloma cell growthen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
ICAQF - Artigos