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MicroRNA-296-5p increases proliferation in gastric cancer through repression of Caudal-related homeobox 1.
MedLine Citation:
PMID:  23353818     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Caudal-related homeobox 1 (CDX1), an intestinal-specific transcription factor, has been reported to have vital roles in gastric intestinal metaplasia (IM). Although IM is a high-risk factor for gastric cancer (GC), the specific role of CDX1 in GC is largely unknown. In this study, we investigated the expression of CDX1 and its functional roles in GC, and its upstream regulatory mechanisms at the microRNA (miRNA) level were further explored. We found that CDX1 is lost in GC when compared with adjacent IM tissues. Gain-of-function studies showed that CDX1 significantly inhibited GC cell growth by inducing cell cycle arrest and apoptosis. Interestingly, we identified and verified an onco-mir, miR-296-5p, as a direct upstream regulator of CDX1. miR-296-5p overexpression significantly promoted GC cell growth and attenuated the CDX1-induced anti-growth effects by recurring cell cycle distribution and apoptotic status, whereas knockdown of miR-296-5p decreased GC cell growth. Furthermore, we found that the extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation and the subsequent downstream changes in protein levels related to cell cycle and apoptosis partly account for the miR-296-5p-CDX1-induced GC growth promotion. In addition, the detection of miR-296-5p and expression of CDX1 in primary GC tissues and adjacent IM tissues revealed that miR-296-5p is inversely correlated with CDX1, further supporting our in vitro results. Our results showed an anti-growth effect of CDX1 and identified its miRNA regulatory mechanism in GC. The identification of this novel miR-296-5p-CDX1-ERK1/2 axis sheds new light on the understanding of the process from IM to GC and may provide therapeutic targets for the treatment of GC.Oncogene advance online publication, 28 January 2013; doi:10.1038/onc.2012.637.
Authors:
T Li; Y Y Lu; X D Zhao; H Q Guo; C H Liu; H Li; L Zhou; Y N Han; K C Wu; Y Z Nie; Y Q Shi; D M Fan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-28
Journal Detail:
Title:  Oncogene     Volume:  -     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
State Key Laboratory of Cancer Biology and Department of Gastroenterology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
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