Mediator MED23 induces premature senescence by interacting with BCLAF1 via blocking autophagy flux in lung cancer cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA597226 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10756542_1.fastq.gz | Fastqsanger.gz | |||
| SRR10756542_2.fastq.gz | Fastqsanger.gz | |||
| SRR10756543_1.fastq.gz | Fastqsanger.gz | |||
| SRR10756543_2.fastq.gz | Fastqsanger.gz | |||
| SRR10756544_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:macroautophagy/autophagy plays a key role in regulating the balance between cell survival and senescence during the progression of lung cancer. Med23 (also known as Sur2), a protein belonging to an evolutionarily conserved high-molecularmass complex composed of more than 20 distinct subunits, promotes the growth, metastasis , and migration of lung cancer cells and is overexpressed in multiple cancers. However, the function of MED23 in autophagy regulation remains unknown. Here, we observes that MED23 expression is significantly upregulated in a subset of cancer cells and reversely correlated with overall survival rates and clinical stage for lung cancer patients. Mechanistically, MED23 is found to interact with BCLAF1 (BCL-2-associated transcription factor 1, BTF) ,a nuclear protein that can induce apoptosis and autophagy. Moreover, BCLAF1 interacts with the promoter of NUPR1 and downregulates its expression. We further show that BCLAF1 and MED23 depletion inhibits autophagy and induces premature senescence in vitro. Remarkably, the expression of BCLAF1 and MED23 are negatively correlated with NUPR1 in the human lung cancer tissues and adjacent normal tissues. Collectively, our data reveal a physical and genetic interaction between BCLAF1 and MED23, suggesting that MED23 constitutes a molecular node in the regulatory network of autophagy and this pathway may be an important therapeutic target in lung cancer.
2019-12-23 | GSE142508 | GEO
Project description:Bcl-2-accociated transcription factor 1(BCLAF1) has been reported to be involved in diverse biological processes. Alternative splicing leads to mutiple transcript virants in human cells and we are interested in functions of its full length isoform(BCLAF1-L) in human colon cancer cells, thus to understanding its role in colon cancer progression. We used microarray to detail the global programme of gene expression after BCLAF1-L knockdown(sh-BCLAF1-L#1) in RKO cells and identified distinct classes of up-regulated or down-regulated genes impaired by its inhibition, when comparing with the control group(sh-Luci). RKO cells were infected with retroviruses either expressing control (sh-Luci) or BCLAF1-L knockdown (sh-BCLAF1-L#1). Medium was replaced 24h after infection, and infected cells were selected by the addition of puromycin (2ug/ml) for 72-96h. Then cells were havested for RNA extraction and hybridization on Affymetrix microarrays.
2013-12-05 | E-GEOD-52990 | biostudies-arrayexpress
Project description:p85beta of the PI3K can localize to the nucleus. Our immunoprecipitation data showed that it physically interacts with a transcription factor BCLAF1. To reveal the enrichment of p85beta and BCLAF1 at genomic regions and to determine whether p85beta and BCLAF1 co-occupy at genomic regions, chromatin immunoprecipitation sequencing (ChIP-seq) was performed.
2024-12-25 | GSE266856 | GEO
Project description:To analysis TCR induced Med23-dependent gene expression programs in T cells, we have employed microarray expression profiling as a discovery platform to identify genes with the potential to be regulated by Med23 in unstimulated or stimulated T cells. Mice CD4 T cells from wildtype and Med23 knockout mice were left unstimulated or stimulated for 6 hr, and gene expression difference was identified among four samples. Expression of seven genes (Med23, IFNg, IL2, Egr2, c-Fos, c-Jun and Foxp1) was validated in the same RNA samples by real-time PCR. TCR induced Med23-dependent gene expression was measured after unstimulation or stimulation for 6 hr in wildtype and Med23 knockout CD4 T cells.
2014-08-27 | E-GEOD-60779 | biostudies-arrayexpress
Project description:Bcl-2-accociated transcription factor 1(BCLAF1) has been reported to be involved in diverse biological processes. Alternative splicing leads to mutiple transcript virants in human cells and we are interested in functions of its full length isoform(BCLAF1-L) in human colon cancer cells, thus to understanding its role in colon cancer progression. We used microarray to detail the global programme of gene expression after BCLAF1-L knockdown(sh-BCLAF1-L#1) in RKO cells and identified distinct classes of up-regulated or down-regulated genes impaired by its inhibition, when comparing with the control group(sh-Luci).
2013-12-05 | GSE52990 | GEO
Project description:p85beta of the PI3K can localize to the nucleus. Our data showed that it can increase the expression of a transcription factor BCLAF1. To determine whether p85beta has any affect on gene transcription and to identify gene targets that are regulated through BCLAF1, RNAseq was performed on p85beta-expressing cells transfected with BCLAF1 siRNA .
2024-12-25 | GSE266499 | GEO
Project description:K-RAS activating mutations occur frequently in non-small cell lung cancer (NSCLC), leading to aberrant activation of Ras-MAPK signaling pathway that contributes to the malignant phenotype. However, the development of Ras-targeted therapeutics remains challenging. Here, we show that MED23, a component of the multisubunit Mediator complex that is known to integrate signaling and gene activities, is selectively important for Ras-active lung cancer. By screening a large panel of human lung cancer cell lines with or without a Ras mutation, we found that Med23 RNAi specifically inhibits the proliferation and tumorigenicity of lung cancer cells with hyperactive Ras activity. Med23-deficiency in fibroblasts selectively inhibited the oncogenic transformation induced by Ras but not by c-Myc. Transcription factor ELK1, which is phosphorylated by MAPK for relaying the Ras signaling to MED23, was also required for the Ras-driven oncogenesis. Transcriptiome analysis revealed that MED23 and ELK1 co-regulate a common set of target genes enriched in regulating cell cycle and proliferation to support the Ras-dependency. Furthermore, correlated with the strength of Ras signaling as indicated by the ELK1 phosphorylation level, MED23 was up-regulated by Ras-transformation, and was found to be overexpressed in both Ras-mutated lung cancer cell lines and primary tumor samples. Remarkably, lower Med23 expression predicts better survival in Ras-active lung cancer patients and xenograft mice. Collectively, our findings demonstrate a critical role for MED23 in enabling the 'Ras-addiction' of lung carcinogenesis, thus providing a vulnerable target for the treatment of Ras-active lung cancer. To gain a genome-wide understanding of how MED23 and ELK1 control gene expression in Ras-active lung cancer cells, we performed gene profiling experiments to analyze the transcriptomes from control, si-Med23, or si-Elk1 A549 cells. The si-Ctrl, si-Med23 and si-Elk1 A549 cells were cultured in the normal condition. Then the cells were harvested for RNA extraction and hybridization on Affymetrix microarrays. The analysis contain 9 samples. si-Ctrl cells have three replicates (si-Ctrl#1, si-Ctrl#2 and si-Ctrl#3), and the si-Med23 or si-Elk1 group contains three different cell lines that harbor three different RNAi oligos against Med23 or Elk1 (si-Med23A, B, C and si-Elk1A, B, C).
2013-08-31 | E-GEOD-40517 | biostudies-arrayexpress
Project description:BCLAF1 is a serine-arginine (SR) protein implicated in transcriptional regulation and mRNA splicing. We have recently identified BCLAF1 as part of a novel mRNA splicing complex that is recruited to different genetic promoters by the breast cancer susceptiblity protein, BRCA1 in response to DNA damage. This ChIP-chip study was designed to identify genes/promoters regulated by the BRCA1/BCLAG1 mRNA splicing complex by identifying promoters bound by BCLAF1 in the absense and presense of BRCA1 in control cells and cells treated with etoposide to induce DNA damage. This study includes tripicate BCLAF1 ChIP-chip experiments in untreated and etoposide treated (1uM 16 hours) control cells (siGFP) and cells depleted of BRCA1 (siBRCA1). Chromatin Immunoprecipitaitons were performed in triplicate with BCLAF1 antibodies in control 293T cells transfected with siGFP siRNAs and BRCA1 siRNAs (siBRCA1 to deplete BRCA1). Immunoprecipitated genomic DNA was labelled with Cy3 and Input genomic DNA was labelled with Cy5 and hybridized to NimbleGen human 3x720k RefSeq promoter arrays to identify BCLAF1 boundgenomic DNA regions.
2014-04-25 | E-GEOD-47016 | biostudies-arrayexpress
Project description:To characterize the function of MED23 on transcription, we generated two MED23-KD 293T cell lines in which MED23 was about 75% knockouted by CRISPR-Cas9. Then we performed RNA-seq to analyze the change of transcript levels around termination sites.
2025-05-28 | GSE211083 | GEO
Project description:we provide evidence that Med23 is involved in the regulation of adult hippocampal neurogenesis in mouse. Med23-deficient NSCs in the SGZ display faster self-renewal activity possibly by reducing cell cycle length, but neuroblasts, immature and mature new-born neurons are reduced.
2020-06-10 | GSE152113 | GEO