Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/202322
Type: Artigo de periódico
Title: Ankhd1 Represses P21 (waf1/cip1) Promoter And Promotes Multiple Myeloma Cell Growth.
Author: Dhyani, Anamika
Machado-Neto, João A
Favaro, Patricia
Saad, Sara T Olalla
Abstract: ANKHD1 (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.
Subject: Ankhd1
Clonogenicity
Multiple Myeloma
Transcriptional Regulation
Tumourigenicity
P21 (waf1/cip1)
Rights: fechado
Identifier DOI: 10.1016/j.ejca.2014.11.012
Address: http://www.ncbi.nlm.nih.gov/pubmed/25483783
Date Issue: 2015
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

Files in This Item:
File SizeFormat 
pmed_25483783.pdf645.36 kBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.