Homo sapiens
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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:Introduction: Amplification at chromosome 8q24 is one of the most frequent genomic abnormalities in human cancers and is associated with reduced survival duration in breast and ovarian cancers. The minimal amplified region encodes c-MYC and the non-coding RNA, PVT1 including miR-1204 encoded in exon 1b. Here we analyzed the genomic changes at chromosome 8q24.21 in breast cancer and the functional roles of miR-1204 in breast and ovarian cancer progression. Methods: The genomic changes at chromosome 8q24.21 were detected in 997 breast cancer tumors and 40 breast cancer cell lines. Expression of miR-1204 in breast and ovarian cancer cell lines was investigated by qRT-PCR method. The role of miR-1204 in the tumorigenesis of breast and ovarian cancer was explored using both knockdown and overexpression of miR-1204 in vitro. Candidate miR-1204 target genes from two independent expression microarray datasets and computational predict programs were identified and further validated by qRT-PCR and western blot methods. The role of inhibition of miR-1204 on tamoxifen sensitivity in breast cancer cells was also investigated. Results: MiR-1204 is frequently co-amplified with MYC and expression of miR-1204 is strongly correlated with the expression and amplification of the noncoding PVT1 transcript and less so with MYC in human breast and ovarian cancer cells. Inhibition of miR-1204 decreases cell proliferation and increased apoptosis in breast and ovarian cancer cell lines with 8q24 amplification, but not in lines without amplification and so may be involved in Myc-induced apoptosis. Additionally, overexpression of miR-1204 enhances both breast and ovarian cancer cell growth and Myc-initiated Rat1A cell transformation. Computational and experimental analyses 30 promising candidate miR-1204 target genes. mRNA levels for these genes were assessed after over expression and knockdown of miR-1204 as were protein levels for 10 genes for which antibodies were available. These studies implicated VDR and ESR1 as miR-1204 targets. Inhibition of miR-1204 increased response to tamoxifen in Estrogen Receptor negative breast cancer cell lines. Conclusions: We conclude that amplification of miR-1204 contributes to breast and ovarian pathophysiology at least in part, by increasing proliferation and down regulating apoptosis and by decreasing expression of VDR and ESR1. Seven cell line sample pairs, where samples are LNA transfected with antimiR-1204 or antimiR-1204 control
2012-04-30 | E-GEOD-37185 | biostudies-arrayexpress