Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA132433 | ENA |
REPOSITORIES: ENA
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Project description:Despite the importance of microRNAs (miRs) for regulation of the delicate balance between cell proliferation and death, only scarce evidence is currently available on their specific involvement during death receptor (DR)-mediated apoptosis. Transfection of mature miR-133b into resistant HeLa cells rendered these sensitive to tumor necrosis factor-alpha (TNFα)-induced cell death. Similarly, miR-133b treatment resulted in exacerbated proapoptotic responses to TNF-related apoptosis-inducing ligand (TRAIL) or an activating antibody to CD95 (Fas/APO1). Comprehensive analysis, encompassing global RNA and protein expression profiling performed by microarray experiments and pulsed stable isotope labeling by amino acids in cell culture (pSILAC), led to the discovery of the antiapoptotic proteins Fas apoptosis inhibitory molecule (FAIM) and glutathione-S-transferase pi (GSTP-1) as immediate miR-133b targets. In-vivo, expression of miR-133b in tumor specimens of prostate cancer patients could be proven as significantly downregulated in 75% of the cases, when compared with matched healthy tissue. Furthermore, introduction of synthetic miR-133b into an ex-vivo model of prostate cancer resulted in impaired proliferation and cellular metabolic activity. These results reveal the ability of a single miR to influence major apoptosis pathways, suggesting an essential role for this molecule during the process of cellular transformation, tumor generation and tissue homeostasis.
2015-01-01 | GSE24613 | GEO
Project description:Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle degeneration. No treatments are currently available to prevent the disease. While the muscle enriched microRNA, miR-133b, has been implicated in muscle biogenesis, its role in DMD remains unknown. To assess miR-133b function in DMD-affected skeletal muscles, we genetically ablated miR-133b in the mdx mouse model of DMD. In the absence of miR-133b, the tibialis anterior muscle of juvenile and adult mdx mice is populated by small muscle fibers and exhibits increased fibrosis, characterized by thickened interstitial space. Additional analysis revealed that loss of miR-133b exacerbates DMD-pathogenesis partly by altering satellite cell numbers and through widespread transcriptomic changes. These include known miR-133b targets as well as genes involved in cell proliferation and fibrosis. Altogether, our data demonstrate that skeletal muscles utilize miR-133b to mitigate the deleterious effects of DMD.
2020-08-15 | GSE156267 | GEO
Project description:miR-92 enhances c-Myc induced apoptosis. In the R26MER/MER mouse embryonic fibroblasts (MEFs), a switchable variant of Myc, MycERT2, was knocked into the genomic region downstream of the constitutive Rosa26 promoter, allowing acute activation of c-Myc by 4-OHT-induced nuclear translocation. This in vitro system nicely recapitulates c-Myc-induced apoptosis, as activated MycERT2 induces strong p53-dependent apoptosis in response to serum starvation. Enforced miR-92 expression in three independent R26MER/MER MEF lines significantly enhanced Myc-induced apoptosis. We used microarrays to investigate the molecular mechanism underlying miR-92 functions. Three independent R26MER/MER MEF lines were infected by MSCV vector alone or by MSCV vector encoding miR-92. These MEFs were serum starved and 4-OHT treated to trigger strong Myc-induced apoptosis.
2013-12-11 | E-GEOD-53225 | biostudies-arrayexpress
Project description:miR-92 enhances c-Myc induced apoptosis. In the R26MER/MER mouse embryonic fibroblasts (MEFs), a switchable variant of Myc, MycERT2, was knocked into the genomic region downstream of the constitutive Rosa26 promoter, allowing acute activation of c-Myc by 4-OHT-induced nuclear translocation. This in vitro system nicely recapitulates c-Myc-induced apoptosis, as activated MycERT2 induces strong p53-dependent apoptosis in response to serum starvation. Enforced miR-92 expression in three independent R26MER/MER MEF lines significantly enhanced Myc-induced apoptosis. We used microarrays to investigate the molecular mechanism underlying miR-92 functions.
2013-12-11 | GSE53225 | GEO
Project description:The microRNA (miR) miR-874, a potential tumour suppressor, causes cell death via target gene suppression in various cancer types. Mevalonate pathway inhibition also causes cell death in breast cancer. However, the relationship between the mevalonate pathway and miR-874-induced apoptosis or its association with the tumour suppressor p53 has not been elucidated. We identified phosphomevalonate kinase (PMVK), a key mevalonate pathway enzyme, and sterol regulatory element-binding factor 2 (SREBF2), the master cholesterol biosynthesis regulator, as direct miR‑874 targets. Next-generation sequencing analysis revealed a significant miR-874–mediated downregulation of PMVK and SREBF2 gene expression and p53 pathway enrichment. Luciferase reporter assays showed that miR-874 directly regulated PMVK and SREBF2. miR-874–induced apoptosis was p53 dependent, and single-cell RNA sequencing analysis demonstrated that miR-874 transfection resulted in apoptosis and p53 pathway activation. Downregulation of PMVK expression also caused cell cycle arrest and p53 pathway activation, which was rescued by geranylgeranyl pyrophosphate (GGPP) supplementation. Analysis of The Cancer Genome Atlas (TCGA) database indicated a negative correlation between miR-874 and PMVK expression and between miR-874 and SREBF2 expression. These findings suggest that miR-874 suppresses the mevalonate pathway by targeting SREBF2 and PMVK, resulting in GGPP depletion, which activates the p53 pathway and promotes cycle arrest or apoptosis.
2022-10-03 | GSE214508 | GEO
Project description:The microRNA (miR) miR-874, a potential tumour suppressor, causes cell death via target gene suppression in various cancer types. Mevalonate pathway inhibition also causes cell death in breast cancer. However, the relationship between the mevalonate pathway and miR-874-induced apoptosis or its association with the tumour suppressor p53 has not been elucidated. We identified phosphomevalonate kinase (PMVK), a key mevalonate pathway enzyme, and sterol regulatory element-binding factor 2 (SREBF2), the master cholesterol biosynthesis regulator, as direct miR‑874 targets. Next-generation sequencing analysis revealed a significant miR-874–mediated downregulation of PMVK and SREBF2 gene expression and p53 pathway enrichment. Luciferase reporter assays showed that miR-874 directly regulated PMVK and SREBF2. miR-874–induced apoptosis was p53 dependent, and single-cell RNA sequencing analysis demonstrated that miR-874 transfection resulted in apoptosis and p53 pathway activation. Downregulation of PMVK expression also caused cell cycle arrest and p53 pathway activation, which was rescued by geranylgeranyl pyrophosphate (GGPP) supplementation. Analysis of The Cancer Genome Atlas (TCGA) database indicated a negative correlation between miR-874 and PMVK expression and between miR-874 and SREBF2 expression. These findings suggest that miR-874 suppresses the mevalonate pathway by targeting SREBF2 and PMVK, resulting in GGPP depletion, which activates the p53 pathway and promotes cycle arrest or apoptosis.
2022-10-03 | GSE214507 | GEO
Project description:We demonstrate that miR-125b, a key node in this microRNA regulatory network, is upregulated in gastric cancer (GC) and associated with poor overall survival through an integrated analysis of microRNA and mRNA profiling of GC revealed a mRNA-regulatory network.So we have employed whole genome microarray expression profiling as a discovery platform to compare the transcriptome profiling of human gastric cells (MKN-45) after 48 hours post-transfection of miR-125b mimic (50nM) and mimic control.Pathway analysis shows that the predicted targets of miR-125b are highly involved in apoptosis/program death pathway，and the robust apoptosis genes, BIK and CASP6 are validated as the directed targets of miR-125b.
2021-02-25 | GSE145959 | GEO
Project description:BACKGROUND & AIMS: Emerging long non-coding RNAs (lncRNAs) have been demonstrated to be associated with progression of various cancers. In the current study, we identified a novel lncRNA-TTN-AS1 and dissected the underlying mechanisms by which lncRNA-TTN-AS1 induced carcinogenesis of esophageal squamous cell carcinoma (ESCC). METHODS: ESCC and adjacent non-malignant specimens from 7 ESCC patients were chosen to analyze the expression profiles of lncRNA-miRNA-mRNA using multiple microarrays. The novel lncRNA-TTN-AS1 was identified using multiple bioinformatics platforms. Levels of lncRNA-TTN-AS1 in tissues from 148 ESCC patients were verified by qRT-PCR and in situ hybridization. The biological function and mechanism of action of lncRNA-TTN-AS1 were performed both in vivo and in vitro using gain-of and loss-of function assays on TE-13 cells and KYSE-410 cells, luciferase reporter assays, RNA immunoprecipitation (RIP) assays and RNA pull-down assays. RESULTS: lncRNA-TTN-AS1 levels were upregulated in ESCC tissues compared with adjacent non-malignant tissues, and correlated with poor prognosis. LncRNA-TTN-AS1, as an oncogene, promoted ESCC cell proliferation and prevented apoptosis. Additionally, lncRNA-TTN-AS1 increased snail1 levels by competitively binding to miR-133b, thereby facilitating epithelial-mesenchymal transition (EMT) cascades. Sharing miR-133b binding sites, lncRNA-TTN-AS1 as a ceRNA also derepressed FSCN1 mediated by miR-133b. Notably, lncRNA-TTN-AS1 stabilized FSCN1 mRNA by interacting directly with the mRNA stabilizing protein HuR, resulting in ESCC invasion-cascades and activation of FSCN1/β-catenin. CONCLUSION: lncRNA-TTN-AS1 sponges miR-133b to govern the expression of snial1 and FSCN1, which promotes ESCC cell proliferation and metastasis. It also combines with HuR to modulate FSCN1 in ESCC cell lines. Our findings may provide a novel target for ESCC anti-metastatic therapies.
2017-03-28 | GSE97050 | GEO
Project description:BACKGROUND & AIMS: Emerging long non-coding RNAs (lncRNAs) have been demonstrated to be associated with progression of various cancers. In the current study, we identified a novel lncRNA-TTN-AS1 and dissected the underlying mechanisms by which lncRNA-TTN-AS1 induced carcinogenesis of esophageal squamous cell carcinoma (ESCC). METHODS: ESCC and adjacent non-malignant specimens from 7 ESCC patients were chosen to analyze the expression profiles of lncRNA-miRNA-mRNA using multiple microarrays. The novel lncRNA-TTN-AS1 was identified using multiple bioinformatics platforms. Levels of lncRNA-TTN-AS1 in tissues from 148 ESCC patients were verified by qRT-PCR and in situ hybridization. The biological function and mechanism of action of lncRNA-TTN-AS1 were performed both in vivo and in vitro using gain-of and loss-of function assays on TE-13 cells and KYSE-410 cells, luciferase reporter assays, RNA immunoprecipitation (RIP) assays and RNA pull-down assays. RESULTS: lncRNA-TTN-AS1 levels were upregulated in ESCC tissues compared with adjacent non-malignant tissues, and correlated with poor prognosis. LncRNA-TTN-AS1, as an oncogene, promoted ESCC cell proliferation and prevented apoptosis. Additionally, lncRNA-TTN-AS1 increased snail1 levels by competitively binding to miR-133b, thereby facilitating epithelial-mesenchymal transition (EMT) cascades. Sharing miR-133b binding sites, lncRNA-TTN-AS1 as a ceRNA also derepressed FSCN1 mediated by miR-133b. Notably, lncRNA-TTN-AS1 stabilized FSCN1 mRNA by interacting directly with the mRNA stabilizing protein HuR, resulting in ESCC invasion-cascades and activation of FSCN1/β-catenin. CONCLUSION: lncRNA-TTN-AS1 sponges miR-133b to govern the expression of snial1 and FSCN1, which promotes ESCC cell proliferation and metastasis. It also combines with HuR to modulate FSCN1 in ESCC cell lines. Our findings may provide a novel target for ESCC anti-metastatic therapies.
2017-03-28 | GSE97049 | GEO
Project description:We used a multi-omics approach combining transcriptomics, proteomics and metabolomics to study the impact of over-expression and inhibition of the microRNA miR-223, a pleiotropic regulator of metabolic-related disease, in the RAW monocyte-macrophage cell line. We analyzed the levels of proteins, mRNAs, and metabolites in order to identify genes involved in miR-223 regulation, to determine candidate disease biomarkers and potential therapeutic targets. We observed that both up- and down-regulation of miR-223 induced profound changes in the mRNA, protein and metabolite profiles in RAW cells. Microarray-based transcriptomics evidenced a change in 120 genes that were linked predominantly to histone acetylation, bone remodeling and RNA regulation. In addition, 30 out the 120 genes encoded long noncoding RNAs. The nanoLC-MS/MS revealed that 52 proteins were significantly altered when comparing scramble, pre- and anti-miR-223 treatments. Sixteen out of the mRNAs coding these proteins genes are predicted to have binding sites for miR-223. CARM-1, Ube2g2, Cactin and Ndufaf4 were confirmed to be miR-223 targets by western blotting. Analyses using Gene Ontology annotations evidenced association with cell death, splicing and stability of mRNAs, bone remodeling and cell metabolism. miR-223 alteration changed the expression of CARM-1, Ube2g2, Cactin and Ndufaf4 during osteoclastogenesis and macrophage, indicating that these genes are potential biomarkers of these processes. The most important discriminant metabolites found in the metabolomics study were found to be hydrophilic amino acids, carboxylic acids linked to metabolism and pyrimidine nucleotides, indicating that changes in miR-223 expression alter the metabolic profile of cells, and may affect their apoptotic and proliferative state.
2021-03-29 | PXD009844 | Pride