Myb-regulated transcriptome in pancreatic cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE61290 | GEO | 2016/05/27
SECONDARY ACCESSION(S): PRJNA261015
REPOSITORIES: GEO
Similar Datasets
Project description:Earlier we have shown important roles of MYB in pancreatic tumor pathobiology. To better understand the role of MYB in the tumor microenvironment and identify MYB-associated secreted biomarker proteins, we conducted mass spectrometry analysis of the secretome from MYB-modulated and control pancreatic cancer cell lines. We also performed in silico analyses to determine MYB-associated biofunctions, gene networks and altered biological pathways. We further investigated the secreted proteins for their potential biomarker properties.
2021-09-08 | PXD015126 | Pride
Project description:We expanded our previously reported transcriptome profiling of K-562 cells (GSE85187) by analyzing the global transcriptional change upon rescue of endogenous MYB knock down (KD) with SUMO-conjugation deficient mutant of MYB (2KR-MYB) and SUMO-binding deficient mutant of MYB (ANAA-MYB) in comparison with K-562 cells treated with siGENOME non-targeting siRNA (GSE85187) , endogenous MYB KD treated with si2992 (GSE85187), rescue of endogenous MYB KD with wild-type MYB (GSE85187) and rescue of endogenous MYB KD with D152V mutant of MYB (GSE85187).
2023-07-17 | GSE124542 | GEO
Project description:Most E2F-binding sites repress transcription through the recruitment of Retinoblasoma (RB) family members until the end of the G1 cell-cycle phase. Although the MYB promoter contains an E2F-binding site, its transcription is activated shortly after the exit from quiescence, before RB family members inactivation, by unknown mechanisms. We had previously uncovered a nuclear factor distinct from E2F, Myb-sp, whose DNA-binding site overlapped the E2F element and had hypothesized that this factor might overcome the transcriptional repression of MYB by E2F-RB family members. We have purified Myb-sp and discovered that Myc-associated zinc finger proteins (MAZ) are major components. We show that various MAZ isoforms are present in Myb-sp and activate transcription via the MYB-E2F element. Moreover, while forced RB or p130 expression repressed the activity of a luciferase reporter driven by the MYB-E2F element, co-expression of MAZ proteins not only reverted repression, but also activated transcription. Finally, we show that MAZ binds the MYB promoter in vivo, that its binding site is critical for MYB transactivation, and that MAZ knockdown inhibits MYB expression during the exit from quiescence. Together, these data indicate that MAZ is essential to bypass MYB promoter repression by RB family members and to induce MYB expression.
2017-10-04 | PXD006857 | Pride
Project description:MYB activation is proposed to underlie development of adenoid cystic cancer (ACC), an aggressive salivary gland tumor with no effective systemic treatments. To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of 12 ACC with matched normal tissues, and compared these data with 14 mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top-scoring gene (18-fold induction), however we observed the same signature in ACC without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among our 12 cases and 3 from public databases) with negligible MYB expression that retained the same ACC mRNA signature including over-expression of extracellular matrix (ECM) genes. Integration of this signature with somatic mutational analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB expression in human salivary gland cells alters cell morphology and cell adhesion in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC tumor culture. In summary, we identified a unique ACC signature with parallel MYB-dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a potential target.
2015-03-13 | GSE59702 | GEO
Project description:MYB activation is proposed to underlie development of adenoid cystic cancer (ACC), an aggressive salivary gland tumor with no effective systemic treatments. To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of 12 ACC with matched normal tissues, and compared these data with 14 mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top-scoring gene (18-fold induction), however we observed the same signature in ACC without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among our 12 cases and 3 from public databases) with negligible MYB expression that retained the same ACC mRNA signature including over-expression of extracellular matrix (ECM) genes. Integration of this signature with somatic mutational analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB expression in human salivary gland cells alters cell morphology and cell adhesion in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC tumor culture. In summary, we identified a unique ACC signature with parallel MYB-dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a potential target.
2015-03-13 | GSE59701 | GEO
Project description:MYB activation is proposed to underlie development of adenoid cystic cancer (ACC), an aggressive salivary gland tumor with no effective systemic treatments. To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of 12 ACC with matched normal tissues, and compared these data with 14 mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top-scoring gene (18-fold induction), however we observed the same signature in ACC without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among our 12 cases and 3 from public databases) with negligible MYB expression that retained the same ACC mRNA signature including over-expression of extracellular matrix (ECM) genes. Integration of this signature with somatic mutational analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB expression in human salivary gland cells alters cell morphology and cell adhesion in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC tumor culture. In summary, we identified a unique ACC signature with parallel MYB-dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a potential target.
2015-03-13 | GSE59700 | GEO
Project description:The Myb proto-oncogene encodes the transcription factor c-MYB, which is critical for the proliferation and differentiation of hematopoietic stem and progenitor cells. Distant enhancers of Myb expression have been characterized but the regulation of Myb during hematopoiesis is still incompletely understood. Here we identified a novel nuclear Myb enhancer long intergenic non-coding RNA (Myrlin) that originates from the -81 kb murine Myb enhancer within the Myb ─ Hbs1l intergenic region. Myrlin and Myb are coordinately regulated in a developmental stage-specific fashion during maturation of erythroid progenitors and upon differentiation of MEL cells. CRISPR/Cas9 genome editing of the Myrlin transcription start site at the -81kb enhancer reduced both Myrlin and Myb expression. The deletion of Myrlin TSS reduces the occupancy of LDB1, which mediates chromatin looping, and compromises long-range contacts between the Myb promoter and enhancer and RNA Pol II occupancy decreases across the Myb locus. In contrast, silencing of Myrlin using CRISPRi similarly reduced both Myrlin and Myb expression but left the Myb enhancer hub undisturbed, separating chromatin looping from transcription activation of Myb. In unedited cells, we found that Myrlin interacts with MLL1 complex, a transcriptional coactivator that plays an essential role in regulating gene expression during hematopoiesis. Myrlin CRISPRi compromised MLL1 occupancy in the Myb locus and decreased CDK9 and RNA Pol II binding. Myrlin CRISPRi further resulted in pausing of RNA Pol II in the Myb first exon/intron. These data suggest that Myrlin directly participates in activating Myb transcription by recruiting MLL1.
2024-06-11 | GSE240060 | GEO
Project description:miR-145 is a tumor suppressor miRNA in various malignancies including pancreatic cancer. How miR-145 regulates expression of other miRNAs could provide a panoramic view of the development of pancreatic cancer. Therefore, in this project, we aimed to characterize how other miRNAs are affected by miR-145 in hope for understanding proteomic changes that are not explained by miR-145 alone. miRNA microarray was used to compare expression of all miRNAs 48 hr after transfection of miR-145 mimics or control scramble RNA in a pancreatic cancer cell line, Mia-PaCa2.
2013-03-19 | E-GEOD-45246 | biostudies-arrayexpress
Project description:Dysregulated gene expression is one of the most prevalent features in human cancers. Here, we show that most subtypes of acute myeloid leukemia (AML) depend on the aberrant assembly of the MYB transcriptional co-activator complex. By rapid and selective peptidomimetic interference with the binding of CBP/P300 to MYB, but not CREB or MLL1, we find that the leukemic functions of MYB are mediated by CBP/P300-mediated co-activation of a distinct set of transcriptional factor complexes that are aberrantly assembled with MYB in AML cells. This therapeutic remodeling is accompanied by dynamic redistribution of CBP/P300 complexes to genes that control cellular differentiation and growth. Thus, aberrantly organized transcription factor complexes control convergent gene expression programs in AML cells. These findings establish a compelling strategy for pharmacologic reprogramming of oncogenic gene expression that supports its targeting for leukemias and other human cancers caused by dysregulated gene control.
2020-12-17 | PXD019708 | Pride