Expression data from miR-224 expressing cells versus control cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE36020 | GEO | 2015/12/31
SECONDARY ACCESSION(S): PRJNA151741
REPOSITORIES: GEO
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Project description:miR-224 is up-regulated in hepatocelluar carcinoma. We mimicked mir-224 over-expression by transfecting 50 nM of miR-224 precursor molecules or control oligos into HCT116 cells with low miR-224 endogenous levels Cells were harvested 24 hours post transfection. Expression profiling was performed on three pairs of miR-224 or control transfected cells from three independent experiments
2015-12-31 | E-GEOD-36020 | biostudies-arrayexpress
Project description:Purpose: Preoperative 5-fluorouracil (5-FU) based radiochemotherapy (RCT) represents the standard treatment for locally advanced rectal cancer. Both, tumor response and progression vary considerably. MicroRNAs represent master regulators of gene expression, and may therefore contribute to this heterogeneity. Results: Thirty-six miRNAs were identified to significantly correlate with sensitivity of CRC cell lines to RCT (q < 0.05). This list included miR320a as most significantly correlated as well as other miRNAs involved in the MAPK-, TGF- and Wnt-pathway. Importantly, transfection of selected miRNAs (let7g, miR-132, miR-224, miR-320a and miR-429) each induced a shift of sensitivity (p<0.00001). Moreover, high expression of miR-224 was associated with a poor prognosis in rectal cancer patients (p=0.043). Experimental design: Genome-wide microRNA (miRNA) profiling was performed from 12 colorectal cancer (CRC) cell lines. To establish an in vitro signature of radiochemosensitivity, these profiles were correlated to the individual sensitivities of each cell line to 5-FU and radiation. The functional relevance of selected miRNAs was validated by transfecting miRNA-mimics into SW480 cells, followed by treatment with 5-FU and radiation. 12 Samples with 3 replicates each.
2013-09-01 | E-GEOD-40976 | biostudies-arrayexpress
Project description:Lung cancer is the leading cause of cancer-related deaths worldwide. Despite advancements and improvements in surgical and medical treatments, the survival rate of lung cancer patients remains frustratingly poor. Local control for early stage non-small cell lung cancer (NSCLC) has dramatically improved over the last decades for both operable and inoperable patients. However, the molecular mechanisms of NSCLC invasion leading to regional and distant disease spread remain poorly understood. Here we identify miR-224 to be significantly up-regulated in NSCLC tissues, in particular in resected NSCLC metastasis. Increased miR-224 expression promotes cell migration, invasion and proliferation by directly targeting the tumor suppressors, TNFAIP1 and SMAD4. In concordance with in vitro studies, mouse xenograft studies validated that miR-224 function as a potent oncomiR in NSCLC in vivo. Moreover, we found promoter hypomethylation and activated ERK signaling to be involved in the regulation of miR-224 expression in NSCLC. Up-regulated mir-224 thus facilitates tumor progression by shifting the equilibrium of the partially antagonist functions of SMAD4 and TNFAIP1 towards enhanced invasion and growth in NSCLC. Our findings indicate that targeting miR-224 could be effective in the treatment of certain lung cancer patients
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Project description:Lung cancer is the leading cause of cancer-related deaths worldwide. Despite advancements and improvements in surgical and medical treatments, the survival rate of lung cancer patients remains frustratingly poor. Local control for early stage non-small cell lung cancer (NSCLC) has dramatically improved over the last decades for both operable and inoperable patients. However, the molecular mechanisms of NSCLC invasion leading to regional and distant disease spread remain poorly understood. Here we identify miR-224 to be significantly up-regulated in NSCLC tissues, in particular in resected NSCLC metastasis. Increased miR-224 expression promotes cell migration, invasion and proliferation by directly targeting the tumor suppressors, TNFAIP1 and SMAD4. In concordance with in vitro studies, mouse xenograft studies validated that miR-224 function as a potent oncomiR in NSCLC in vivo. Moreover, we found promoter hypomethylation and activated ERK signaling to be involved in the regulation of miR-224 expression in NSCLC. Up-regulated mir-224 thus facilitates tumor progression by shifting the equilibrium of the partially antagonist functions of SMAD4 and TNFAIP1 towards enhanced invasion and growth in NSCLC. Our findings indicate that targeting miR-224 could be effective in the treatment of certain lung cancer patients Oncogenic role of miR-224 in lung cancer
2015-07-01 | E-GEOD-64859 | biostudies-arrayexpress
Project description:Purpose: Available tools for prostate cancer (PC) diagnosis and prognosis are suboptimal and novel biomarkers are urgently needed. Here, we investigated the regulation and biomarker potential of the GABRE~miR-452~miR-224 genomic locus. Experimental design: GABRE/miR-452/miR-224 transcriptional expression was quantified in 80 non-malignant and 281 PC tissue samples. GABRE promoter methylation was determined by methylation-specific qPCR (MethyLight) in 35 non-malignant, 293 PC (radical prostatectomy (RP) cohort 1) and 198 PC tissue samples (RP cohort 2). Diagnostic/prognostic biomarker potential of GABRE methylation was evaluated by ROC, Kaplan-Meier, uni- and multivariate Cox regression analyses. Functional roles of miR-224 and miR-452 were investigated in PC3 and DU145 cells by viability, migration, and invasion assays and gene-set enrichment analysis (GSEA) of post-transfection transcriptional profiling data. Results: GABRE~miR-452~miR-224 was significantly downregulated in PC compared to non-malignant prostate tissue and had highly cancer-specific aberrant promoter hypermethylation (AUC=0.98). Functional studies and GSEA suggested that miR-224 and miR-452 inhibit proliferation, migration, and invasion of PC3 and DU145 cells by direct/indirect regulation of pathways related to the cell cycle and cellular motility. Finally, in uni- and multivariate analyses, high GABRE promoter methylation was significantly associated with biochemical recurrence in RP cohort 1, which was successfully validated in RP cohort 2. Conclusion: The GABRE~miR-452~miR-224 locus is downregulated and hypermethylated in PC and is a new promising epigenetic candidate biomarker for PC diagnosis and prognosis. Tumor suppressive functions of the intronic miR-224 and miR-452 were demonstrated in two PC cell lines, suggesting that epigenetic silencing of GABRE~miR-452~miR-224 may be selected for in PC.
2013-12-11 | GSE51053 | GEO
Project description:Purpose: Available tools for prostate cancer (PC) diagnosis and prognosis are suboptimal and novel biomarkers are urgently needed. Here, we investigated the regulation and biomarker potential of the GABRE~miR-452~miR-224 genomic locus. Experimental design: GABRE/miR-452/miR-224 transcriptional expression was quantified in 80 non-malignant and 281 PC tissue samples. GABRE promoter methylation was determined by methylation-specific qPCR (MethyLight) in 35 non-malignant, 293 PC (radical prostatectomy (RP) cohort 1) and 198 PC tissue samples (RP cohort 2). Diagnostic/prognostic biomarker potential of GABRE methylation was evaluated by ROC, Kaplan-Meier, uni- and multivariate Cox regression analyses. Functional roles of miR-224 and miR-452 were investigated in PC3 and DU145 cells by viability, migration, and invasion assays and gene-set enrichment analysis (GSEA) of post-transfection transcriptional profiling data. Results: GABRE~miR-452~miR-224 was significantly downregulated in PC compared to non-malignant prostate tissue and had highly cancer-specific aberrant promoter hypermethylation (AUC=0.98). Functional studies and GSEA suggested that miR-224 and miR-452 inhibit proliferation, migration, and invasion of PC3 and DU145 cells by direct/indirect regulation of pathways related to the cell cycle and cellular motility. Finally, in uni- and multivariate analyses, high GABRE promoter methylation was significantly associated with biochemical recurrence in RP cohort 1, which was successfully validated in RP cohort 2. Conclusion: The GABRE~miR-452~miR-224 locus is downregulated and hypermethylated in PC and is a new promising epigenetic candidate biomarker for PC diagnosis and prognosis. Tumor suppressive functions of the intronic miR-224 and miR-452 were demonstrated in two PC cell lines, suggesting that epigenetic silencing of GABRE~miR-452~miR-224 may be selected for in PC. Affymetrix GeneChip Human Gene 1.0 ST Arrays were used for whole-genome transcriptional profiling of DU145 and PC3 cells at 48 hours post-transfection with either miR-224, miR-452, or scrambled miRNA mimics, or untransfected. All experiments were performed in duplicate. Transcript expression levels were determined after RMA16 normalization in GeneSpringGX 11.0 software (Agilent). PC3 and DU145 arrays were normalized separately. DU145 48 t Scr2a were excluded from the study because of bad performance of this microarray.
2013-12-11 | E-GEOD-51053 | biostudies-arrayexpress
Project description:A summary of the work associated to these microarrays is the following: MicroRNAs (miRNAs) are small non-coding RNAs involved in RNA silencing that play a role in many biological processes. They are involved in the development of many diseases, including cancer. Extensive experimental data show that they play a role in the pathogenesis of cancer as well as the development of drug resistance during treatment. MiRNA microarrays of sensitive and MTX-resistant HT29 colon cancer cells were performed. The results were analyzed using the GeneSpring GX11.5 software. Differentially expressed microRNAs in resistant cells were identified and miR-224, which was greatly underexpressed and displayed robust raw signal values, was selected for further studies. Putative targets were predicted using TargetScan 5.1 software and intersected with the data from expression microarrays previously performed. This approach allowed us to identify miR-224 targets that were differentially expressed more than 2-fold in resistant cells. Among them, ARL3, CDS2, DCP2, HSPC159, MYST3 and SLC4A4 were validated at the mRNA level by qRT-PCR. Functional assays using an anti-miR against miR-224 desensitized the cells toward MTX, mimicking the resistant phenotype. On the other hand, siRNA treatment against SLC4A4 or incubation of Poly Purine Reverse Hoogsteen (PPRH) hairpins against CDS2 or HSPC159 increased sensitivity to MTX. These results revealed a role for miR-224 and its targets in MTX resistance in HT29 colon cancer cells. KEYWORDS Methotrexate, miRNAs, drug resistance, DHFR
2013-05-29 | GSE28547 | GEO
Project description:A summary of the work associated to these microarrays is the following: MicroRNAs (miRNAs) are small non-coding RNAs involved in RNA silencing that play a role in many biological processes. They are involved in the development of many diseases, including cancer. Extensive experimental data show that they play a role in the pathogenesis of cancer as well as the development of drug resistance during treatment. MiRNA microarrays of sensitive and MTX-resistant HT29 colon cancer cells were performed. The results were analyzed using the GeneSpring GX11.5 software. Differentially expressed microRNAs in resistant cells were identified and miR-224, which was greatly underexpressed and displayed robust raw signal values, was selected for further studies. Putative targets were predicted using TargetScan 5.1 software and intersected with the data from expression microarrays previously performed. This approach allowed us to identify miR-224 targets that were differentially expressed more than 2-fold in resistant cells. Among them, ARL3, CDS2, DCP2, HSPC159, MYST3 and SLC4A4 were validated at the mRNA level by qRT-PCR. Functional assays using an anti-miR against miR-224 desensitized the cells toward MTX, mimicking the resistant phenotype. On the other hand, siRNA treatment against SLC4A4 or incubation of Poly Purine Reverse Hoogsteen (PPRH) hairpins against CDS2 or HSPC159 increased sensitivity to MTX. These results revealed a role for miR-224 and its targets in MTX resistance in HT29 colon cancer cells. KEYWORDS Methotrexate, miRNAs, drug resistance, DHFR Two cell lines are compared in the study, which are HT29 colon cancer cells sensitive to methotrexate and HT29 cells resistant to 10e-5M MTX. Six samples are provided which correspond to 3 samples for the control condition and 3 samples for the resistant condition. Data files from miRNA and mRNA (previously submitted to GEO as GSE11440) microarrays were analyzed with GeneSpring GX11.5 software (Agilent Technologies) to find differentially expressed miRNAs and their cellular target genes in the resistant cell lines compared to their sensitive counterparts.
2013-05-29 | E-GEOD-28547 | biostudies-arrayexpress
Project description:Purpose: Preoperative 5-fluorouracil (5-FU) based radiochemotherapy (RCT) represents the standard treatment for locally advanced rectal cancer. Both, tumor response and progression vary considerably. MicroRNAs represent master regulators of gene expression, and may therefore contribute to this heterogeneity. Results: Thirty-six miRNAs were identified to significantly correlate with sensitivity of CRC cell lines to RCT (q < 0.05). This list included miR320a as most significantly correlated as well as other miRNAs involved in the MAPK-, TGF- and Wnt-pathway. Importantly, transfection of selected miRNAs (let7g, miR-132, miR-224, miR-320a and miR-429) each induced a shift of sensitivity (p<0.00001). Moreover, high expression of miR-224 was associated with a poor prognosis in rectal cancer patients (p=0.043).
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Project description:Women with diabetes have a higher prevalence of cardiovascular complications than men, suggesting that sex-steroid hormones like estrogen may impact on female health in diabetes. Here we demonstrate that estrogen suppletion and insulin resistance in male-to-female transgenders coincides with lower plasma levels of miR-224 and miR-452 carried in extracellular vesicles. Systemic silencing of miR-224 and miR-452 in mice triggered a prediabetic phenotype with higher plasma insulin levels, increased white adipose lipogenesis and less glucose uptake and mitochondrial respiration in brown adipose tissue. Consistent with a prediabetic metabolic state, RNA sequencing demonstrated differential expression of genes involved in lipogenesis in white adipose tissue and mitochondrial respiration and glucose uptake in brown adipose tissue. In vitro studies confirmed the estrogen-dependent lowering of miR-224 (brown adipocytes) and miR-452 (white adipocytes) and their impact on adipocyte-specific metabolic processes. Collectively, we identified novel estrogen-driven, post-transcriptional networks that could drive the progression to insulin resistance in transwomen and provide potential anti-diabetic therapeutic targets in women.
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