MUC1-C represses the RASSF1A tumor suppressor and activated Kras signaling in human carcinoma cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA510078 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8318500.fastq.gz | Fastqsanger.gz | |||
| SRR8318501.fastq.gz | Fastqsanger.gz | |||
| SRR8318492.fastq.gz | Fastqsanger.gz | |||
| SRR8318502.fastq.gz | Fastqsanger.gz | |||
| SRR8318493.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:RASSF1A encodes a tumor suppressor that inhibits RAS’RAF’MEK’ERK signaling and is one of the most frequently inactivated genes in human cancers. MUC1-C is an oncogenic effector of the cancer cell epigenome that is overexpressed in diverse carcinomas. We show here that MUC1-C represses RASSF1A expression in multiple types of KRAS wild-type and mutant cancer cells. Mechanistically, MUC1-C occupies the RASSF1A promoter in a complex with the ZEB1 transcriptional repressor. In turn, MUC1-C/ZEB1 complexes recruit DNA methyltransferase 3b (DNMT3b) to the CpG island in the RASSF1A promoter. Targeting MUC1-C, ZEB1 and DNMT3b thus decreases methylation of the CpG island and derepresses RASSF1A transcription. We also show that targeting MUC1-C downregulates KRAS signaling with decreases in MEK/ERK activation, which is of importance for RAS-mediated tumorigenicity. These findings define a previously unrecognized role for MUC1-C in suppression of RASSF1A and support targeting MUC1-C as an approach for inhibiting KRAS signaling.
2019-05-27 | GSE123860 | GEO
Project description:KRAS activation drives DNA methylation and silencing of specific tumor suppressor genes (TSGs). We previously showed that the ERK pathway induces transcriptional repression of TET1, which results in conversion of TSG promoters from a hydroxymethylated, active state to a hypermethylated and silenced state. Here we identified miR-29b as a KRAS-induced molecule that represses TET1 expression. In KRAS-transformed cells, ectopic miR-29b inhibition restores expression of TET1, thereby reactivating TSGs by reducing methylation and restoring hydroxymethylation. Mining gene expression data of lung cancer cell lines identified additional TSGs suppressed by KRAS signaling whose expression was restored by inhibition of miR-29b and re-expression of TET1. Because KRAS changes TSG promoters from hydroxymethylated to hypermethylated with miR-29b-dependent silencing of TET1, we demonstrate a model in which DNMT1 is present on target promoters prior to KRAS transformation. We also propose miR-29b as a potential circulating biomarker and target for rational treatment of specific malignancies.
2017-07-31 | GSE100857 | GEO
Project description:This is a phase II Randomized comparison clinical trial of activated CIK armed with anti-CD3-MUC1 bispecific antibody for advanced colorectal cancer. And the aim of this research is to study the clinical efficacy and safety of activated CIK armed with anti-CD3-MUC1 bispecific antibody for colorectal cancer.
| 2272861 | ecrin-mdr-crc
Project description:Mucin 1 (MUC1) is a transmembrane mucin expressed at the apical surface of epithelial cells at different mucosal surfaces including breast and intestine. The MUC1 extracellular domain contains a variable number of tandem repeats (VNTR) of 20 amino acids, which are heavily O-linked glycosylated. Monoclonal antibodies against the MUC1 VNTR can be powerful tools because of their multiplicity of binding and possible applications in the diagnosis and treatment of MUC1-expressing cancers. One such antibody is the hybridoma mouse monoclonal 139H2 which is also widely used as a research tool to study non-cancer MUC1. Here we report direct mass spectrometry-based sequencing of hybridoma-derived 139H2 IgG, which enabled reverse engineering of a recombinant 139H2.
2024-03-18 | PXD043489 | Pride
Project description:The MUC1-C protein evolved in mammals for adaptation of barrier tissues to loss of homeostasis. Prolonged activation of MUC1-C in settings of chronic inflammation promotes lineage plasticity, epigenetic reprogramming and the cancer stem cell (CSC) state. The effects of MUC1-C on the metabolism of CSCs remain unexplored. The present studies performed on purified populations of triple-negative breast cancer (TNBC) CSCs demonstrate that MUC1-C integrates the capacity for self-renewal with the activation of aerobic glycolysis. We show that MUC1-C is essential for (i) CSC mammosphere formation and tumorigenicity and (ii) activation of GLUT1, HK2 and other glycolytic genes. We further show that MUC1-C activates nuclear genes that encode components of mitochondrial Complexes II-V of the electron transfer chain (ETC). Of importance, MUC1-C also represses mitochondrial DNA (mtDNA) genes encoding components of Complexes I-V. The observed involvement of MUC1-C in the suppression of mtDNA genes is explained by MUC1-C-mediated (i) downregulation of the mitochondrial transcription factor A (TFAM), which is required for mtDNA transcription, and (ii) induction of the mitochondrial transcription termination factor 3 (mTERF3). In support of this pathway to suppress mitochondrial ROS production, targeting MUC1-C increases (i) mtDNA gene transcription, (ii) superoxide levels and (iii) loss of self-renewal capacity. These findings indicate that MUC1-C regulates CSC self-renewal and redox balance by integrating activation of glycolysis with suppression of oxidative phosphorylation.
2023-10-11 | GSE222377 | GEO
Project description:RASSF1A encodes a tumor suppressor that inhibits the RAS→RAF→MEK→ERK pathway and is one of the most frequently inactivated genes in human cancers. MUC1-C is an oncogenic effector of the cancer cell epigenome that is overexpressed in diverse carcinomas. We show here that MUC1-C represses RASSF1A expression in KRAS wild-type and mutant cancer cells. Mechanistically, MUC1-C occupies the RASSF1A promoter in a complex with the ZEB1 transcriptional repressor. In turn, MUC1-C/ZEB1 complexes recruit DNA methyltransferase 3b (DNMT3b) to the CpG island in the RASSF1A promoter. Targeting MUC1-C, ZEB1, and DNMT3b thereby decreases methylation of the CpG island and derepresses RASSF1A transcription. We also show that targeting MUC1-C regulates KRAS signaling, as evidenced by RNA-seq analysis, and decreases MEK/ERK activation, which is of importance for RAS-mediated tumorigenicity. These findings define a previously unrecognized role for MUC1-C in suppression of RASSF1A and support targeting MUC1-C as an approach for inhibiting MEK→ERK signaling.
| S-EPMC6872931 | biostudies-literature
Project description:Goal of study: To determine differentially expressed genes with potential roles in tolerance and immunity in MUC1-immunized WT and MUC1.Tg mice WT (C57Bl/6) and MUC1.Tg mice were immunized (i.v.) with dendritic cells loaded with sythetic, human MUC1 peptide. At 24h and 72h splenic RNA from vaccination groups (n=3) was pooled and microarray performed.
2013-01-16 | E-GEOD-43503 | biostudies-arrayexpress
Project description:To determine if overexpression of MUC1 alters the microRNA profile of pancreatic cancer cells S2.013. Comparison of miRNAs differentially regulated in pancreatic cancer cell line S2.013 with and without MUC1 overexpression. MiRCURY LNA microarray was used to determine differential microRNA expression in one replicate of S2.013.Neo (control) cells compared to S2.013.MUC1 (experimental) cells. Confirmation with qRT-PCR was performed on a subset of microRNAs identified as differentially regulated between the two groups.
2013-08-10 | E-GEOD-48185 | biostudies-arrayexpress
Project description:The aberrant overexpression of mucin 1 (MUC1) and human epidermal growth factor receptor 2 (HER2) are often observed in breast cancer. However, the role of concomitant of MUC1/HERR2 in the development of breast cancer has not been fully illustrated. Following analysis public microarray datasets that revealed a correlation of double positive of MUC1 and HER2 to a worse clinical outcome, we generated a mouse model overexpressing both Her2 and MUC1 cytoplasmic domain (MUC1-CD) to investigate their interaction in mammary carcinogenesis. Coexpression of Her2 and MUC1-CD confers growth advantage and promotes the development of spontaneous mammary tumors. Genomic analysis uncovers that enforced expression of MUC1-CD and Her2 induces mammary tumor lineage plasticity which is supported by gene reprogramming and mammary stem cell enrichment. With gain- and loss-of function strategies, we show that coexpression of Her2 and MUC1-CD was associated with down-regulation of TCA cycle genes in tumors. Importantly, the reduction of TCA cycle genes induced by MUC1-CD is is significantly connected to the poor prognosis in HER2+ breast cancer patients. In addition, MUC1 augments Her2 signaling pathway by inducing Her2/Egfr dimerization. These findings collectively demonstrate the vital role of MUC1-CD/Her2 collaboration in shaping mammary tumor landscape and highlight the prognostic and therapeutic implication of MUC1 in patients with Her2+ breast cancer.
2022-03-10 | GSE198239 | GEO
Project description:We identified a novel E2 ubiquitin conjugating activity within the C-terminus domain of MUC1. To determine if E2 ubiquitin conjugating activity of MUC1 is responsible for regulating expression of oncogenic genes we isolated RNA from vector control cells, MUC1 wildtype overexpression cells, and cells that express a serine mutant lacking E2 activity. RNA was isolated from each of the 3 cell lines, S2013.Neo, S2013.MUC1-WT, and S2013.MUC1-Ser. Gene expression was analyzed by spotted microarray and the differences in gene expression were calculated between the cell lines
2016-08-01 | E-GEOD-60339 | biostudies-arrayexpress