Characterization of miR-34 effectors in colorectal cancer cells.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE227230 | GEO | 2023/08/21
REPOSITORIES: GEO
Similar Datasets
Project description:p53 inactivation occurs only rarely in neuroblastoma, although miR-34, a transcriptional target of p53, is often deleted in neuroblastoma, suggesting another way in which p53 signaling might be impaired. In this study we show that miR-34 directly targets and downregulates the Polycomb Repressive Complex 2 (PRC2) and its associated histone demethylase, JARID1A, in a p53-dependent manner, 4 samples were transfected with miRNA control or miR-34a, miR-34b, miR-34c into SK-N-BE2 cells.
2014-01-01 | E-GEOD-49845 | biostudies-arrayexpress
Project description:The miR-34 family of microRNAs consisting of miR-34a, miR-34b and miR-34c are tumour suppressors. The annotated human miR-34b-5p has one additional base at the 5’ end of the common miR-34 family seed sequence, compared to miR-34a-5p and miR-34c-5p. This extra base results in a shift of the seed sequence, which would affect the target gene repertoire and have functional consequences. During our studies of miR-34 functions, we investigated the precise sequence of mature miR-34b-5p in human cells by deep sequencing. We found that a miR-34b-5p without the extra base was the predominant form in both non-malignant and malignant cells derived from several human tissues, indicating that the miR-34b annotation is misleading. We evaluated the functional implications of the seed shift, by comparing the effect of mimics representing the alternative miR-34b-5p sequences in MDA-MB-231 cells. In contrast to the annotated miR-34b, the endogenously expressed miR-34b displayed tumour suppressive characteristics in vitro similarly to miR-34c. These data demonstrate the importance of determining the precise sequence of a mature microRNA before exploring miRNA functions.
2017-09-14 | GSE98601 | GEO
Project description:We used microarrays to detail the global programme of gene expression that occurs in response to miR-449 or miR-34 overexpression in proliferating HAECs. Each donors were transfected with pre-miR-Negative control, pre-miR-449a and pre-miR-449b. The donors 3 and 4 were morever transfected with pre-miRs-34 (34a, 34b-5p, 34c-5p).
2011-06-06 | E-GEOD-22143 | biostudies-arrayexpress
Project description:Expression of the miR-34 family (miR-34a, -34b, -34c) is elevated in settings of heart disease, and inhibition with antimiR-34a/antimiR-34 has emerged as a promising therapeutic strategy. Under chronic cardiac disease settings, targeting the entire miR-34 family is more effective than targeting miR-34a alone. The identification of transcription factor (TF)-miRNA regulatory networks has added complexity to understanding the therapeutic potential miRNA-based therapies. Here, we sought to determine whether antimiR-34 targets secondary miRNAs via TFs which could contribute to antimiR-34-mediated protection. Using miRNA-Seq we identified differentially regulated miRNAs in hearts from mice with cardiac pathology due to transverse aortic constriction (TAC), and these miRNAs were also regulated by antimiR-34. Two clusters of stress-responsive miRNAs were classified as “pathological” and “cardioprotective”. Using ChIPBase we identified 45 TF binding sites on the promoters of “pathological” and “cardioprotective” miRNAs, and 5 represented direct targets of miR-34, with the capacity to regulate other miRNAs. The expression of two “pathological” miRNAs (let-7e and miR-31) was independently experimentally validated in hearts from antimiR-34 treated TAC mice, and may explain why targeting the entire miR-34 family is more effective than targeting miR-34a alone. AntimiR-34 regulates the expression of other miRNAs and this has significant implications for drug development.
2016-05-08 | GSE79050 | GEO
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 28 hpf with or without treatment with a DNA-damaging drug camptothecin. The results of this RNA-seq experiments showed that the loss of miR-34a does not strongly affect induction of genes by DNA-damage. However, the overall pattern of gene expression is significantly different as shown by Principal Component Analysis and there is a group of about 100 genes which are differentially expressed due to loss of miR-34a. The dataset we present in this submission was used to reach these conclusions.
2019-12-21 | GSE142440 | GEO
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: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:miR-34a and miR-34b/c genes are frequently epigenetically silenced in primary CRCs. However, the in vivo relevance of miR-34a/b/c for suppression of intestinal tumor formation has not been analyzed by genetic approaches. ApcMin/+ mice with deletion of the miR-34a and miR-34b/c genes were generated and analyzed. The mRNA expression profiles of intestinal adenomas with and without functional miR-34a/b/c genes were compared.
2017-05-28 | GSE84138 | GEO
Project description:p53 inactivation occurs only rarely in neuroblastoma, although miR-34, a transcriptional target of p53, is often deleted in neuroblastoma, suggesting another way in which p53 signaling might be impaired. In this study we show that miR-34 directly targets and downregulates the Polycomb Repressive Complex 2 (PRC2) and its associated histone demethylase, JARID1A, in a p53-dependent manner,
2014-01-01 | GSE49854 | GEO
Project description:p53 inactivation occurs only rarely in neuroblastoma, although miR-34, a transcriptional target of p53, is often deleted in neuroblastoma, suggesting another way in which p53 signaling might be impaired. In this study we show that miR-34 directly targets and downregulates the Polycomb Repressive Complex 2 (PRC2) and its associated histone demethylase, JARID1A, in a p53-dependent manner,
2014-01-01 | GSE49845 | GEO