Project description:To evaluate the differential potential affected by SMARCE1 -MD/MD(R42A) , we performed RNA-sequencing (RNA-seq) of Smarce1-MD and control Smarce1-MD (R42A) embrynoic body.
Project description:Reactivation of the telomerase reverse transcriptase subunit, TERT, is linked to tumourigenesis due to well-documented telomere-dependent and independent functions. The aim of this study was to investigate the effect of the telomerase inhibitor, MST-312, on TERT functions, focusing in particular, on its effects on MYC stabilty and MYC-regulated pathways, in order to assess its potential as a therapeutic agent. We demonstrate that MST-312 reduces MYC levels in cancer cells, leading to reduced MYC levels on chromatin, and subsequently affecting the MYC-regulated transcriptional program. As a result, MST-312 treatment increases the survival of lymphoma-bearing mice. Mechanistically, MST-312 affects the conformation of TERT, leading to TERT/Terc dissociation, and the subsequent loss of both its telomere-dependent and independent functions. Based on the presented data, we conclude that MST-312 treatment is a promising therapeutic strategy, in particular, in MYC-driven tumorus.
Project description:Reactivation of the telomerase reverse transcriptase subunit, TERT, is linked to tumourigenesis due to well-documented telomere-dependent and independent functions. The aim of this study was to investigate the effect of the telomerase inhibitor, MST-312, on TERT functions, focusing in particular, on its effects on MYC stabilty and MYC-regulated pathways, in order to assess its potential as a therapeutic agent. We demonstrate that MST-312 reduces MYC levels in cancer cells, leading to reduced MYC levels on chromatin, and subsequently affecting the MYC-regulated transcriptional program. As a result, MST-312 treatment increases the survival of lymphoma-bearing mice. Mechanistically, MST-312 affects the conformation of TERT, leading to TERT/Terc dissociation, and the subsequent loss of both its telomere-dependent and independent functions. Based on the presented data, we conclude that MST-312 treatment is a promising therapeutic strategy, in particular, in MYC-driven tumorus.
Project description:To evaluate the effects of mitotic degradation of SMARCE1 upon gene expression, we performed RNA-sequencing (RNA-seq) of cultures of four independent subclones each of Smarce1-MD and control Smarce1-MD (R42A) mESCs. We found that transcription of the core pluripotency regulatory network was not disrupted. In contrast, GO analysis showed that neural differentiation-associated terms were enriched among genes upregulated in Smarce1-MD mESCs. To better understand the difference in neural fates in the neural induction experiments, we performed differential gene expression analysis and gene set enrichment analysis (GSEA) studies. Mitotic degradation of SMARCE1 resulted in higher expression of GABA receptors and hyper-activation of synaptic signaling on neural induction, indicating the aberrant neural cell fate commitment compared to SMARCE1-MD (R42A) cultures. And then we add back BMP4 to partically rescue the phenotype and very small amount of BMP4 will rescue the phenotype.
