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Author (up) Althoff, K.; Beckers, A.; Odersky, A.; Mestdagh, P.; Koster, J.; Bray, I.M.; Bryan, K.; Vandesompele, J.; Speleman, F.; Stallings, R.L.; Schramm, A.; Eggert, A.; Sprussel, A.; Schulte, J.H.
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  Title MiR-137 functions as a tumor suppressor in neuroblastoma by downregulating KDM1A Type Journal Article
  Year 2013 Publication International Journal of Cancer. Journal International du Cancer Abbreviated Journal Int J Cancer  
  Volume 133 Issue 5 Pages 1064-1073  
  Keywords Lsd1; epigenetics; miR-137; neuroblastoma  
  Abstract Neuroblastoma is the most common extracranial solid tumor of childhood, and accounts for approximately 15% of all childhood cancer deaths. The histone demethylase, lysine-specific demethylase 1 (KDM1A, previously known as LSD1), is strongly expressed in neuroblastomas, and overexpression correlates with poor patient prognosis. Inducing differentiation in neuroblastoma cells has previously been shown to down regulate KDM1A, and siRNA-mediated KDM1A knockdown inhibited neuroblastoma cell viability. The microRNA, miR-137, has been reported to be downregulated in several human cancers, and KDM1A mRNA was reported as a putative target of miR-137 in colon cancer. We hypothesized that miR-137 might have a tumor-suppressive role in neuroblastoma mediated via downregulation of KDM1A. Indeed, low levels of miR-137 expression in primary neuroblastomas correlated with poor patient prognosis. Re-expressing miR-137 in neuroblastoma cell lines increased apoptosis and decreased cell viability and proliferation. KDM1A mRNA was repressed by miR-137 in neuroblastoma cells, and was validated as a direct target of miR-137 using reporter assays in SHEP and HEK293 cells. Furthermore, siRNA-mediated KDM1A knockdown phenocopied the miR-137 re-expression phenotype in neuroblastoma cells. We conclude that miR-137 directly targets KDM1A mRNA in neuroblastoma cells, and activates cell properties consistent with tumor suppression. Therapeutic strategies to re-express miR-137 in neuroblastomas could be useful to reduce tumor aggressiveness.  
  Address Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, Essen, Germany  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0020-7136 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23400681 Approved no  
  Call Number @ @ Serial 42043  
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