Profiling of microRNA expression in lung cancer cells with up-regulation of Zeb1
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE38386 | GEO | 2012/08/09
SECONDARY ACCESSION(S): PRJNA167760
REPOSITORIES: GEO
Similar Datasets
Project description:The Zeb1 transcriptional repressor plays a key role in metastasis through the down-regulation of genes that are strong inducers of epithelial differentiation and inhibitors of stem-ness. Here we report that Zeb1 controls the expression of numerous oncogenic and tumor suppressive microRNAs (miRs). Zeb1 stimulated pro-migratory cytoskeletal processes by down-regulating miR-34a and activated Rho GTPases through Arhgap1, a Cdc42 GTPase activating protein and novel miR-34a target gene. Poor-prognosis human lung adenocarcinomas were highly enriched in a cytoskeletal gene signature activated by miR-34a down-regulation. These findings suggest that Zeb1 regulates a miR network and drives pro-migratory cytoskeletal processes through miR-34a. Microarray-based interrogation of global miR expression changes in a non-metastatic KP cell line (393P) that undergoes EMT and gains invasive and metastatic capabilities following forced Zeb1 expression (393P_Zeb1). two group comparison
2012-08-08 | E-GEOD-38386 | biostudies-arrayexpress
Project description:The Zeb1 transcriptional repressor plays a key role in metastasis through the down-regulation of genes that are strong inducers of epithelial differentiation and inhibitors of stem-ness. Here we report that Zeb1 controls the expression of numerous oncogenic and tumor suppressive microRNAs (miRs). Zeb1 stimulated pro-migratory cytoskeletal processes by down-regulating miR-34a and activated Rho GTPases through Arhgap1, a Cdc42 GTPase activating protein and novel miR-34a target gene. Poor-prognosis human lung adenocarcinomas were highly enriched in a cytoskeletal gene signature activated by miR-34a down-regulation. These findings suggest that Zeb1 regulates a miR network and drives pro-migratory cytoskeletal processes through miR-34a.
2012-08-09 | GSE38341 | GEO
Project description:The Zeb1 transcriptional repressor plays a key role in metastasis through the down-regulation of genes that are strong inducers of epithelial differentiation and inhibitors of stem-ness. Here we report that Zeb1 controls the expression of numerous oncogenic and tumor suppressive microRNAs (miRs). Zeb1 stimulated pro-migratory cytoskeletal processes by down-regulating miR-34a and activated Rho GTPases through Arhgap1, a Cdc42 GTPase activating protein and novel miR-34a target gene. Poor-prognosis human lung adenocarcinomas were highly enriched in a cytoskeletal gene signature activated by miR-34a down-regulation. These findings suggest that Zeb1 regulates a miR network and drives pro-migratory cytoskeletal processes through miR-34a. Total RNA was extracted from primary tumors from mice injected with 344SQ-vector and -miR-34a cells, and then hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 array. Determination of differentially expressed genes was carried out.
2012-08-08 | E-GEOD-38341 | biostudies-arrayexpress
Project description:MiR-34a appears to be protective against cancer. Blocking miR-34a results in pro-tumorigenic phenotypic changes. The purpose of this experiment was to identify gene expression changes that could potentially explain the pro-tumorigenic effects of anti-miR 34a transfection.
2017-07-05 | GSE59182 | GEO
Project description:MicroRNAs (miRNAs or miRs) are small, noncoding RNAs that are implicated in the regulation of nearly all biological processes. Global miRNA biogenesis is altered in many cancers and RNA-binding proteins (RBPs) have been shown to play a role in this process, presenting a promising avenue for targeting miRNA dysregulation in disease. miR-34a exhibits tumor-suppressive functions by targeting cell cycle regulators CDK4/6 and anti-apoptotic factor Bcl-2, among other regulatory pathways such as Wnt, TGF-, and Notch signaling. Many cancers show downregulation or loss of miR-34a, and synthetic miR-34a supplementation has been shown to inhibit tumor growth in vivo; however, the post-transcriptional mechanisms by which miR-34a is lost in cancer are not entirely understood. Here, we have used a proteomics-mediated approach to identify Squamous cell carcinoma antigen recognized by T-cells 3 (SART3) as a putative pre-miR-34a-binding protein. SART3 is a spliceosome recycling factor and nuclear RBP with no previously reported role in miRNA regulation. We demonstrate that SART3 binds pre-miR-34a with specificity over pre-let-7d and begin to elucidate a new functional role for this protein in non-small lung cancer cells. Overexpression of SART3 led to increased miR-34a levels, downregulation of the miR-34a target genes CDK4 and CDK6, and cell cycle arrest in the G1 phase. In vitro binding studies showed that the RNA-recognition motifs within the SART3 sequence are responsible for selective pre-miR-34a binding. Collectively, our results present evidence for an influential role of SART3 in miR-34a biogenesis and cell cycle progression.
2019-10-14 | PXD015278 | Pride
Project description:Li-Fraumeni syndrome (LFS) is a disorder due to inherited mutations in the TP53 gene resulting in an increased risk of developing several types of cancer. MicroRNA miR-34a has been implicated downstream of p53 on the basis of being a direct transcriptional target and, when over-expressed, having pro-apoptotic phenotypes in cell lines. Moreover, miR-34a has been shown to be a modifier gene in the context of LFS, since its epigenetic silencing increases the likelihood of tumour development in patients with mutant TP53. However, the in vivo consequences of miR-34 loss are still unclear. For example, mice lacking all three (a,b,c) miR-34 homologs show no detectable abnormalities in p53 responses. The relative expression of different miR-34 genes in zebrafish was studied using qRT-PCR with specific assays. The miR-34a, miR-34b and miR-34c display unique onset of developmental expression and expression levels, with miR-34a being the most abundant and constant in expression. All of the miR-34 genes also showed clear induction by p53 when DNA-damaging treatments are performed. Using CRISPR-Cas9 technology, we generated a zebrafish miR-34a deletion mutant to further investigate the roles of miR-34a on its own and its association with the p53 pathway. Predictably, a miR-34a deletion mutant demonstrated absence of miR-34a, though without miR-34b and miR-34c compensation beyond baseline expression levels. Mutants survive to adulthood, show no overt phenotypes and have normal apoptotic responses to DNA-damaging irradiation or camptothecin treatments. To further explore the effects of miR-34a, we performed gene expression profiling using RNA-seq of wild-type and miR-34a deletion mutant zebrafish embryos at 8 hpf. This experiment was motivated by a previous report knock-down of miR-34a in zebrafish leads to dramatic increases in expression of miR-34a target genes. We therefore expected that this experiment will help define the set of miR-34a target genes. The results of this RNA-seq experiment showed that the loss of miR-34a led to large transcriptomic effects at 8 hpf (1573 genes UP and 1679 genes DOWN at 1.5-fold change and FDR < 0.05). There was no significant enrichment of predicted miR-34a target genes among the differentially regulated genes but some interesting biological trends were found and will be described in the paper associated with this dataset.
2022-06-14 | GSE205752 | GEO
Project description:Cell lines of a vGPCR-driven tumor model have been compared to identify KSHV-vGPCR-dependent mechanisms of tumor progression. Cell lines include two biological replicates of a vGPCR-transformed tumor cell line (vGPCR-TC#1+#2) generated by passaging a vGPCR-BALB/c-3T3 cell line (also included) through athymic nude and BALB/c mice. A vGPCR-knockdown tumor cell line (derived from vGPCR-TC#1 generated by lentiviral knockdown) and a GFP-transduced control BALB/c-3T3 cell line are included as well. Data also include a vGPCR-TC#1-derived cell line were miR-34a-5p was knocked down using a Tough Decoy RNA, called TuDmiR-34a-TC#1. Additionally, two miR-34a overexpressing cell lines have been generated derived from the parental vGPCR-3T3 cells and the tumor cell line vGPCR-TC#2 named miR-34a-vGPCR-3T3 respectively miR-34a-vGPCR-TC#2.
2016-02-09 | E-MTAB-3393 | biostudies-arrayexpress
Project description:Li-Fraumeni syndrome (LFS) is a disorder due to inherited mutations in the TP53 gene resulting in an increased risk of developing several types of cancer. MicroRNA miR-34a has been implicated downstream of p53 on the basis of being a direct transcriptional target and, when over-expressed, having pro-apoptotic phenotypes in cell lines. Moreover, miR-34a has been shown to be a modifier gene in the context of LFS, since its epigenetic silencing increases the likelihood of tumour development in patients with mutant TP53. However, the in vivo consequences of miR-34 loss are still unclear. For example, mice lacking all three (a,b,c) miR-34 homologs show no detectable abnormalities in p53 responses. The relative expression of different miR-34 genes in zebrafish was studied using qRT-PCR with specific assays. The miR-34a, miR-34b and miR-34c display unique onset of developmental expression and expression levels, with miR-34a being the most abundant and constant in expression. All of the miR-34 genes also showed clear induction by p53 when DNA-damaging treatments are performed. Using CRISPR-Cas9 technology, we generated a zebrafish miR-34a deletion mutant to further investigate the roles of miR-34a on its own and its association with the p53 pathway. Predictably, a miR-34a deletion mutant demonstrated absence of miR-34a, though without miR-34b and miR-34c compensation beyond baseline expression levels. Mutants survive to adulthood, show no overt phenotypes and have normal apoptotic responses to DNA-damaging irradiation or camptothecin treatments. To further explore the effects of miR-34a, we performed gene expression profiling using RNA-seq of wild-type and miR-34a deletion mutant zebrafish embryos at 72 hpf. We wanted to explore how miR-34a loss affects differentiated organs in larval zebrafish. This resulted in 389 genes UP and 374 genes DOWN at 1.5-fold change and FDR < 0.05. There was no significant enrichment of predicted miR-34a target genes among the differentially regulated genes but some interesting biological trends were found and will be described in the paper associated with this dataset.
2022-06-14 | GSE205754 | GEO
Project description:The goal of this study was to determine the role of miR-34a in regulating chondrocyte transcript profiles. Next Generation Sequencing of total RNA extracted from mouse KO and WT chondrocytes revealed 175 significantly differentially expressed genes (84 up, 91 down) in miR-34a KO chondrocytes compared to WT cells. We are currently validating potential direct targets of miR-34a from our NGS data and performing computational pathway analysis to identify novel pathways regulated by miR-34a.
2021-03-08 | GSE133775 | GEO
Project description:Altered by defects in p53, epigenetic silencing, and genomic loss, the microRNA miR-34a represents one of the most clinically relevant tumor-suppressive microRNAs. Without question, a striking number of patients with cancer would benefit from miR-34a replacement, if poor miR-34a stability, non-specific delivery, and delivery-associated toxicity could be overcome. Here, we highlight a fully modified version of miR-34a (FM-miR-34a) that overcomes these hurdles when conjugated to a synthetically simplistic ligand. FM-miR-34a is orders of magnitude more stable than a partially modified version, without compromising its activity, leading to stronger repression of a greater number of miR-34a targets. FM-miR-34a potently inhibited proliferation and invasion, and induced sustained downregulation of endogenous target genes for >120 hours following in vivo delivery. In vivo targeting was achieved through conjugating FM-miR-34a conjugated to folate (FM-FolamiR-34a), which inhibited tumor growth leading to complete cures in some mice. These results have the ability to revitalize miR-34a as an anti-cancer agent, providing a strong rationale for clinical testing.
2023-09-05 | GSE237836 | GEO