Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA109937 | ENA |
REPOSITORIES: ENA
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Project description:Cell cycle arrest in response to DNA damage is an important anti-tumorigenic mechanism. microRNAs (miRNAs) were shown recently to play key regulatory roles in cell cycle progression. For example, miR-34a is induced in response to p53 activation and mediates G1 arrest by down-regulating multiple cell cycle-related transcripts. Here we show that genotoxic stress promotes the p53-dependent up-regulation of the homologous miRNAs, miR -192 and miR-215. Like miR-34a, activation of miR-192/215 induces cell cycle arrest suggesting that multiple microRNA families operate in the p53 network. Furthermore, we define a downstream gene expression signature for miR-192/215 expression that includes a number of transcripts that regulate G1 and G2 checkpoints. Of these transcripts, 18 transcripts are direct targets of miR-192/215 and the observed cell cycle arrest likely results from a cooperative effect among the modulations of these genes by the miRNAs. Our results demonstrating a role for miR-192/215 in cell proliferation combined with recent observations that these miRNAs are under-expressed in primary cancers support the idea that miR-192 and miR-215 function as tumor-suppressors.
2008-12-07 | GSE13105 | GEO
Project description:Cell cycle arrest in response to DNA damage is an important anti-tumorigenic mechanism. microRNAs (miRNAs) were shown recently to play key regulatory roles in cell cycle progression. For example, miR-34a is induced in response to p53 activation and mediates G1 arrest by down-regulating multiple cell cycle-related transcripts. Here we show that genotoxic stress promotes the p53-dependent up-regulation of the homologous miRNAs, miR -192 and miR-215. Like miR-34a, activation of miR-192/215 induces cell cycle arrest suggesting that multiple microRNA families operate in the p53 network. Furthermore, we define a downstream gene expression signature for miR-192/215 expression that includes a number of transcripts that regulate G1 and G2 checkpoints. Of these transcripts, 18 transcripts are direct targets of miR-192/215 and the observed cell cycle arrest likely results from a cooperative effect among the modulations of these genes by the miRNAs. Our results demonstrating a role for miR-192/215 in cell proliferation combined with recent observations that these miRNAs are under-expressed in primary cancers support the idea that miR-192 and miR-215 function as tumor-suppressors. Description: Transfection of siRNA luc, miR-192 or miR-215 into HCT116 Dicerex5, compared to mock-transfected cells, with mRNA expression profiled at 10h and 24h post-transfection. Species: Human Tissue: HCT116 Dicerex5 cell line (tissue of origin = human colorectal carcinoma); this cell line is hypomorphic for Dicer gene function. Dye-swap: no Negative control: siRNA luc Replicates per each timepoint: no
2010-06-24 | E-GEOD-13105 | biostudies-arrayexpress
Project description:p53 suppresses tumor progression and metastasis by regulating a large set of genes and microRNAs. By profiling 92 primary hepatocellular carcinomas (HCCs) and 9 HCC cell lines, we found that p53 upregulates microRNAs including miR-200 and miR-192 family members.
2011-05-11 | GSE28661 | GEO
Project description:p53 suppresses tumor progression and metastasis by regulating a large set of genes and microRNAs. By profiling 92 primary hepatocellular carcinomas (HCCs) and 9 HCC cell lines, we found that p53 upregulates microRNAs including miR-200 and miR-192 family members. By sequencing TP53 in 92 HCC samples, we classified the 92 samples into two groups (wt and mut). We also classified 9 HCC cell lines by testing p21 expression after DNA-damage mediated p53 activation. We then profiled microRNA expression in 92 HCC tissue samples and 9 HCC celll lines to identify p53-regulated microRNAs.
2011-05-11 | E-GEOD-28661 | biostudies-arrayexpress
Project description:Heterotrimeric guanine nucleotide-binding proteins (G proteins) transmit extracellular signals from cell surface G protein-coupled receptors to intracellular effector molecules. Attention has been paid to the Gα12 family members because they mediate cell invasion, migration, and tumorigenesis. In our findings, Gα12 levels were higher in human HCCs than non-tumorous liver tissues. Array analyses using Huh7 cells stably transfected with Gα12QL (an active mutant form) enabled us to extract the microRNAs dysregulated by Gα12 active mutant. Of them, miR-122 was most greatly decreased. In addition, we found decreases of miR-200b/a, miR-192/215 levels. Dysregulation of the microRNAs changed the levels of key proteins associated with HCC cell migration/invasion.
2014-02-04 | GSE44079 | GEO
Project description:MicroRNAs are a class of non-coding short-chained RNAs that control cellular functions by downregulating their target genes. Recent research indicates that microRNAs play a role in the maintenance of gut homeostasis. miR-215 was found to be highly expressed in epithelial cells of the small intestine; however, the involvement of miR-215 in gut immunity remains unknown. Here, we show that miR-215 negatively regulates inflammation in the small intestine by inhibiting CXCL12 production. Mice lacking miR-215 showed high susceptibility to inflammation induced by indomethacin, accompanied by an increased number of Th17 cells in the lamina propria of the small intestine. Our findings support a promising perspective of targeting miR-215 to treat inflammatory conditions in the small intestine.
2022-01-27 | GSE186708 | GEO
Project description:MicroRNAs have been demonstrated to be deregulated in multiple myeloma (MM). We have previously reported the downregulation of miR-214 in MM compared to normal plasma cells. In the present study, we have explored the functional role of miR-214 in myeloma pathogenesis. Ectopic expression of miR-214 reduced cell growth and induced apoptosis of myeloma cells. In order to identify the potential direct target genes of miR-214 which could be involved in the biological pathways regulated by this miRNA, gene expression profiling of H929 myeloma cell line transfected with precursor miR-214 was carried out. Functional analysis revealed significant enrichment for DNA replication, cell cycle phase and DNA binding. We show that miR-214 directly down-regulates the expression of PSMD10, which encodes the oncoprotein gankyrin, and ASF1B, a histone chaperone required for DNA replication, by binding to their 3'-UTR. In addition, gankyrin inhibition induced an increase of P53 mRNA levels and subsequent up-regulation in CDKN1A (p21Waf1/Cip1) and BAX transcripts, which are direct transcriptional targets of p53. In conclusion, we demonstrate that miR-214 function as a tumor suppressor in myeloma by a positive regulation of p53 and inhibition of DNA replication.
2012-12-28 | GSE35948 | GEO
Project description:MicroRNAs have been demonstrated to be deregulated in multiple myeloma (MM). We have previously reported the downregulation of miR-214 in MM compared to normal plasma cells. In the present study, we have explored the functional role of miR-214 in myeloma pathogenesis. Ectopic expression of miR-214 reduced cell growth and induced apoptosis of myeloma cells. In order to identify the potential direct target genes of miR-214 which could be involved in the biological pathways regulated by this miRNA, gene expression profiling of H929 myeloma cell line transfected with precursor miR-214 was carried out. Functional analysis revealed significant enrichment for DNA replication, cell cycle phase and DNA binding. We show that miR-214 directly down-regulates the expression of PSMD10, which encodes the oncoprotein gankyrin, and ASF1B, a histone chaperone required for DNA replication, by binding to their 3'-UTR. In addition, gankyrin inhibition induced an increase of P53 mRNA levels and subsequent up-regulation in CDKN1A (p21Waf1/Cip1) and BAX transcripts, which are direct transcriptional targets of p53. In conclusion, we demonstrate that miR-214 function as a tumor suppressor in myeloma by a positive regulation of p53 and inhibition of DNA replication. H929 cell line was transfected with Pre-miR™ miRNA precursors pre-miR-214 or pre-miR™ miRNA negative, non-targeting control#1 (Ambion) at 50 nM concentration, using the nucleofector II system with C-16 program (Amaxa). The experiments were performed in triplicates.
2012-12-28 | E-GEOD-35948 | biostudies-arrayexpress
Project description:Heterotrimeric guanine nucleotide-binding proteins (G proteins) transmit extracellular signals from cell surface G protein-coupled receptors to intracellular effector molecules. Attention has been paid to the GM-NM-112 family members because they mediate cell invasion, migration, and tumorigenesis. In our findings, GM-NM-112 levels were higher in human HCCs than non-tumorous liver tissues. Array analyses using Huh7 cells stably transfected with GM-NM-112QL (an active mutant form) enabled us to extract the microRNAs dysregulated by GM-NM-112 active mutant. Of them, miR-122 was most greatly decreased. In addition, we found decreases of miR-200b/a, miR-192/215 levels. Dysregulation of the microRNAs changed the levels of key proteins associated with HCC cell migration/invasion. Huh7 hepatoma cells were transfected with pCMV or the plasmid encoding for activated mutant of GM-NM-112 (GM-NM-112QL). Stable transfectants were selected by incubating the cells in culture medium containing Geneticin for 3 weeks. We performed a miRNA microarray for the identification of global microRNA expression changes using WT-Huh7 and Huh7-GM-NM-112QL cells. RNA for each set was harvested from quadruple plates.
2014-02-04 | E-GEOD-44079 | biostudies-arrayexpress
Project description:Deficient DNA repair capacity is associated with genetic lesions accumulation and susceptibility to carcinogenesis. MicroRNAs (miRNAs) are small non-coding RNAs that regulate various cellular pathways including DNA repair. Here we hypothesized that the existence of HBV products may interfere with cellular nucleotide excision repair (NER) through microRNA-mediated gene regulation. We found that NER was impaired in HepG2.2.15 cells, a stable HBV-expressing cell line, compared with its parental cell line HepG2. Altered miRNA expression profile, in particular the significant upregulation of miR-192, was observed in HepG2.2.15 cells. Additionally, ERCC3 and ERCC4, two key factors implicated in NER, were identified as targets of miR-192 and over-expressing miR-192 significantly inhibited cellular NER. These results indicated that persistent HBV infection might trigger NER impairment in part through upregulation of miR-192, which suppressed the levels of ERCC3 and ERCC4. It provides new insight into the effect of chronic HBV infection on NER and genetic instability in cancer.
2011-08-03 | GSE27561 | GEO