Journal ArticleDOI
Identification of miR-145 and miR-146a as mediators of the 5q– syndrome phenotype
Daniel T. Starczynowski,Florian Kuchenbauer,Bob Argiropoulos,Sandy Sung,Ryan D. Morin,Andrew L Muranyi,Martin Hirst,Donna E. Hogge,Marco A. Marra,Richard A. Wells,Rena Buckstein,Wan L. Lam,R. Keith Humphries,Aly Karsan +13 more
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TLDR
Deletes chromosome 5q and identifies Toll–interleukin-1 receptor domain–containing adaptor protein (TIRAP) and tumor necrosis factor receptor–associated factor-6 (TRAF6) as respective targets of these miRNAs.Abstract:
5q- syndrome is a subtype of myelodysplastic syndrome characterized by severe anemia and variable neutropenia but normal or high platelet counts with dysplastic megakaryocytes. We examined expression of microRNAs (miRNAs) encoded on chromosome 5q as a possible cause of haploinsufficiency. We show that deletion of chromosome 5q correlates with loss of two miRNAs that are abundant in hematopoietic stem/progenitor cells (HSPCs), miR-145 and miR-146a, and we identify Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP) and tumor necrosis factor receptor-associated factor-6 (TRAF6) as respective targets of these miRNAs. TIRAP is known to lie upstream of TRAF6 in innate immune signaling. Knockdown of miR-145 and miR-146a together or enforced expression of TRAF6 in mouse HSPCs resulted in thrombocytosis, mild neutropenia and megakaryocytic dysplasia. A subset of mice transplanted with TRAF6-expressing marrow progressed either to marrow failure or acute myeloid leukemia. Thus, inappropriate activation of innate immune signals in HSPCs phenocopies several clinical features of 5q- syndrome.read more
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Journal ArticleDOI
Integrated analysis of miRNAome and transcriptome reveals miRNA-mRNA network regulation in Vibrio alginolyticus infected thick shell mussel Mytilus coruscus.
TL;DR: In this article, an integrated analysis of miRNAome and transcriptome was performed to reveal miRNA-mRNA network regulation in Vibrio alginolyticus infected M. coruscus.
Posted ContentDOI
Post-transcriptional Regulation is the Major Driver of microRNA Expression Variation
TL;DR: The model that, on the global level, post-transcriptional regulation dominates over transcriptional regulation in determining mature miRNA expression patterns in both normal tissues and cancer is reported, suggesting that there are groups of miRNAs that are co-regulated on the post- transcriptional level.
Patent
Soluble cd33 for treating myelodysplastic syndromes (mds)
List Alan F,Sheng Wei +1 more
TL;DR: In this article, compositions and methods for treating disease or condition caused or exacerbated by S100A9 activity, such as myelodysplastic syndromes (MDS) using a composition comprising an effective amount of a CD33/S100A 9 inhibitor are presented.
Dissertation
Physiological and Pharmacological Regulation of the STAT3 Pathway in Cancer
TL;DR: Atovaquone is established as a novel STAT3 inhibitor with evidence of anti-cancer efficacy in patients and a new mechanism of crosstalk between STAT3 and NF-κB relevant to constitutive STAT3 activation in malignancy and the role of inflammation in oncogenesis is indicated.
Journal ArticleDOI
Cytogenetic place in managing myelodysplastic syndromes: an update by the Groupe francophone de cytogénétique hématologique (GFCH).
Virginie Eclache,Marina Lafage-Pochitaloff,Christine Lefebvre,Dominique Penther,Sophie Raynaud,Isabelle Tigaud +5 more
TL;DR: New techniques including next generation sequencing revealed somatic driver mutations especially those affecting genes involved in RNA splicing or those harboring important prognostic value (TP53, ASXL1…) with potential applications in clinical practice in the future.
References
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