TXNIP loss increases Myc genomic occupancy [ChIP-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE208412 | GEO | 2023/02/07
REPOSITORIES: GEO
Similar Datasets
Project description:Our Myc ChIP sequencing result demonstrated that TXNIP loss increased Myc genomic occupancy levels. To determine whether TXNIP loss increased Myc genomic occupancy through increasing chromatin accessibility for Myc binding, we performed assay for transposase-accessible chromatin with sequencing (ATAC-seq) on parental 231 and 231:TKO cells.
2023-02-07 | GSE222672 | GEO
Project description:To better understand how TXNIP in the contributes to the poor prognosis of triple-negative breast cancers, our lab has generated TXNIP null MDA-MB-231 cells (231:TKO). We characterized the gene exrpession programs of these cells by RNA-seq. To determine the Myc-dependence of the transcriptional programs of 231:TKO cells, we used an siRNA RNA approach to reduce Myc levels.
2023-02-07 | GSE208415 | GEO
Project description:To examine the generality of our finding where the gene expression profile of TXNIP knockout in MDA-MB-231 cells resembles of that Myc overexpression transcriptional program, our lab has generated TXNIP null HCC70 (HCC70:TKO) and MB135 (MB135:TKO) cells. We characterized the gene exrpession programs of these cells by RNA-seq.
2023-02-07 | GSE222693 | GEO
Project description:Imatinib is highly effective in the treatment of chronic myelogenous leukemia (CML), but the primary and acquired imatinib resistance remains the big hurdle. Molecular mechanisms for CML resistance to tyrosine kinase inhibitors, beyond point mutations in BCR-ABL kinase domain, still need to be addressed. Here, we demonstrated that TXNIP is a novel BCR-ABL target gene. Suppression of TXNIP is responsible for BCR-ABL triggered glucose metabolic reprogramming and mitochondrial homeostasis. Mechanistically, Miz-1/P300 complex transactivates TXNIP through the recognition of TXNIP core promoter region, responding to the c-Myc suppression by either imatinib or BCR-ABL knockdown. TXNIP restoration sensitizes CML cells to imatinib treatment and compromises imatinib resistant CML cell survival, predominantly through the blockage of both glycolysis and glucose oxidation which results in the mitochondrial dysfunction and ATP production. In particular, TXNIP suppresses expressions of the key glycolytic enzyme, HK2 and LDHA, potentially through Fbw7-dependent c-Myc degradation. In accordance, BCR-ABL suppression of TXNIP provides a novel survival pathway for the transformation of mouse BM cells. Combination of drug inducing TXNIP expression with imatinib synergistically kills CML cells from patients and further extends the survival of CML mice. Thus, the activation of TXNIP represents an effective strategy for CML treatment to overcome resistance.
2023-05-03 | GSE218451 | GEO
Project description:In human breast cancer, mortality is associated with metastasis to distant sites. Therefore, it is critical to elucidate the biological mechanisms that underlie tumor progression and metastasis. Using signaling pathway signatures we previously predicted a role for E2F transcription factors in Myc induced tumors. To test this role we interbred MMTV-Myc transgenic mice with E2F knockouts. Surprisingly, we observed that the loss of E2F2 sharply increased the percentage of lung metastasis in MMTV-Myc transgenic mice. Examining the gene expression profile from these tumors, we identified genetic components that were potentially involved in mediating metastasis. These genes were filtered to uncover the genes involved in metastasis that also impacted distant metastasis free survival in human breast cancer. In order to elucidate the mechanism by which E2F2 loss enhanced metastasis we generated knockdowns of E2F2 in MDA-MB-231 cells and observed increased migration in vitro and increased lung colonization in vivo. We then examined genes that were differentially regulated between tumors from MMTV-Myc, MMTV-Myc E2F2-/-, and lung metastases samples and identified PTPRD. To test the role of PTPRD in E2F2-mediated breast cancer metastasis, we generated a knockdown of PTPRD in MDA-MB-231 cells. We noted that decreased levels of PTPRD resulted in decreased migration in vitro and decreased lung colonization in vivo. Taken together, these data indicate that E2F2 loss results in increased metastasis in breast cancer, potentially functioning through a PTPRD dependent mechanism. Lung metastases from MMTV-Myc tumors in a E2F2 knockout and E2F3 +/- backgrounds were analyzed for their gene expression profile
2016-08-08 | E-GEOD-71815 | biostudies-arrayexpress
Project description:Txnip C247S Mouse Heart Analysis
| PRJNA699847 | ENA
Project description:Cardiomyocyte specific knock in mouse heart with Txnip Cysteine 247 to Serine Mutation
2021-02-06 | GSE166252 | GEO
Project description:Purpose: To identifiy mRNA changes in wt cone photoreceptors with Txnip overexpression treatment, which improved retinitis pigmentosa (RP) cone survival and visual acuity. Methods: two wt mouse strains, BALB/c and C57BL/6J were injected with AAV-Txnip or AAV-H2BGFP control subretinally at P0. Retinas were dissected out at P21 for BALB/c and P35 for C57BL/6J. 1,000 H2BGFP labeled cones per retina sample were FACS sorted out, and subject for RNA-sequencing. Results: only ~70 genes in P21 BALB/c and 1 genes in C57BL/6J were found differentially expressed with Txnip treatment. Only 1 genes (i.e. Txnip) were in commonly upregulated between the two lists. Conclusions: Txnip seems to be not changing RNA expression much in wt cones. Instead, its major function to rescue RP cones may lay in protein-protein interactions.
2021-03-15 | GSE168503 | GEO
Project description:Txnip deficient mice with hepatocellular carcinoma
2007-12-04 | E-GEOD-2127 | biostudies-arrayexpress
Project description:In human breast cancer, mortality is associated with metastasis to distant sites. Therefore, it is critical to elucidate the biological mechanisms that underlie tumor progression and metastasis. Using signaling pathway signatures we previously predicted a role for E2F transcription factors in Myc induced tumors. To test this role we interbred MMTV-Myc transgenic mice with E2F knockouts. Surprisingly, we observed that the loss of E2F2 sharply increased the percentage of lung metastasis in MMTV-Myc transgenic mice. Examining the gene expression profile from these tumors, we identified genetic components that were potentially involved in mediating metastasis. These genes were filtered to uncover the genes involved in metastasis that also impacted distant metastasis free survival in human breast cancer. In order to elucidate the mechanism by which E2F2 loss enhanced metastasis we generated knockdowns of E2F2 in MDA-MB-231 cells and observed increased migration in vitro and increased lung colonization in vivo. We then examined genes that were differentially regulated between tumors from MMTV-Myc, MMTV-Myc E2F2-/-, and lung metastases samples and identified PTPRD. To test the role of PTPRD in E2F2-mediated breast cancer metastasis, we generated a knockdown of PTPRD in MDA-MB-231 cells. We noted that decreased levels of PTPRD resulted in decreased migration in vitro and decreased lung colonization in vivo. Taken together, these data indicate that E2F2 loss results in increased metastasis in breast cancer, potentially functioning through a PTPRD dependent mechanism.
2016-08-08 | GSE71815 | GEO