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10.1371/journal.pone.0136843 http://scihub22266oqcxt.onion/10.1371/journal.pone.0136843 C4552723!4552723 !26317501     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26317501 &cmd=llinks): Failed to open stream: HTTP request failed! 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Targeting the Sonic Hedgehog-Gli1 Pathway as a Potential New Therapeutic Strategy for Myelodysplastic Syndromes |pdf=|usr=}}{{26317501 }} gab.com Text Targeting the Sonic Hedgehog-Gli1 Pathway as a Potential New Therapeutic Strategy for Myelodysplastic Syndromes JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=26317501 #FOAvip The complex mechanistic array underlying the pathogenesis of myelodysplastic syndrome (MDS) is still unclear. Although dysregulations of different signaling pathways involved in MDS have been described, the identification of specific biomarkers and therapy targets remains an important task in order to establish novel therapeutic approaches. Here, we demonstrated that the Shh signaling pathway is active in MDS and correlated it with disease progression. Additionally, the knockdown of Gli1 significantly inhibited cell proliferation in vitro and in vivo. Gli1 silencing also induced apoptosis and G0/G1 phase arrest. Furthermore, Gli1 silencing enhanced the demethylating effect of 5-aza-2'-deoxycytidine on the p15 gene promoter and subsequently promoted its expression by inhibiting DNA methyltransferase 1(DNMT1). Our findings show that the Shh signaling pathway plays a role in the pathogenesis and disease progression of MDS, and proceeds by modulating DNA methylation. This pathway may prove to be a potential therapeutic target for enhancing the therapeutic effects of 5-azacytidine on malignant transformation of MDS. Twit Text FOAVip Targeting the Sonic Hedgehog-Gli1 Pathway as a Potential New Therapeutic Strategy for Myelodysplastic Syndromes ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=26317501 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26317501 #FOAvip English Wikipedia <ref>{{Cite pmid|26317501 }}</ref> Targeting the Sonic Hedgehog-Gli1 Pathway as a Potential New Therapeutic Strategy for Myelodysplastic Syndromes #MMPMID26317501 Zou J ; Zhou Z ; Wan L ; Tong Y ; Qin Y ; Wang C ; Zhou K PLoS One 2015[]; 10 (8 ): e0136843 PMID26317501 show ga The complex mechanistic array underlying the pathogenesis of myelodysplastic syndrome (MDS) is still unclear. Although dysregulations of different signaling pathways involved in MDS have been described, the identification of specific biomarkers and therapy targets remains an important task in order to establish novel therapeutic approaches. Here, we demonstrated that the Shh signaling pathway is active in MDS and correlated it with disease progression. Additionally, the knockdown of Gli1 significantly inhibited cell proliferation in vitro and in vivo. Gli1 silencing also induced apoptosis and G0/G1 phase arrest. Furthermore, Gli1 silencing enhanced the demethylating effect of 5-aza-2'-deoxycytidine on the p15 gene promoter and subsequently promoted its expression by inhibiting DNA methyltransferase 1(DNMT1). Our findings show that the Shh signaling pathway plays a role in the pathogenesis and disease progression of MDS, and proceeds by modulating DNA methylation. This pathway may prove to be a potential therapeutic target for enhancing the therapeutic effects of 5-azacytidine on malignant transformation of MDS. |Adolescent [MESH] |Adult [MESH] |Aged [MESH] |Animals [MESH] |Azacitidine/analogs & derivatives/pharmacology [MESH] |Cell Line, Tumor [MESH] |Cell Survival/drug effects [MESH] |Cyclin-Dependent Kinase Inhibitor p15/genetics/metabolism [MESH] |DNA Methylation/drug effects [MESH] |DNA Modification Methylases/pharmacology [MESH] |Decitabine [MESH] |Female [MESH] |Gene Expression Regulation, Neoplastic/drug effects [MESH] |Hedgehog Proteins/*antagonists & inhibitors/*genetics [MESH] |Humans [MESH] |Male [MESH] |Mice [MESH] |Middle Aged [MESH] |Myelodysplastic Syndromes/*drug therapy/genetics/metabolism/*pathology [MESH] |Neoplasm Transplantation [MESH] |Prognosis [MESH] |Promoter Regions, Genetic/drug effects [MESH] |Signal Transduction/drug effects [MESH] |Transcription Factors/*genetics/metabolism [MESH] |Young Adult [MESH]Targeting the Sonic Hedgehog-Gli1 Pathway as a Potential New Therapeut(epmc).pdf DeepDyve Pubget Overpricing