Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few therapeutic options available to cancer patients. MicroRNA 21-5p (miR-21) has been shown to be upregulated in HCC, but the contribution of this oncomiR to the maintenance of tumorigenic phenotype in liver cancer remains poorly understood. We have developed potent and specific single-stranded oligonucleotide inhibitors of miR-21 (anti-miRs) and used them to interrogate dependency on miR-21 in a panel of liver cancer cell lines. Treatment with anti-miR-21, but not with a mismatch control anti-miR, resulted in significant de-repression of direct targets of miR-21 and led to loss of viability in the majority of HCC cell lines tested. Robust induction of caspase activity, apoptosis and necrosis was noted in anti-miR-21 treated HCC cells. Furthermore, ablation of miR-21 activity resulted in inhibition of HCC cell migration and suppression of clonogenic growth. To better understand the consequences of miR-21
Anti-miR-21 Suppresses Hepatocellular Carcinoma Growth via Broad Transcriptional Network Deregulation.
Cell line
View SamplesStem cells reside in specific niches providing stemness-maintaining environments. Thus, the regulated migration from these niches is associated with differentiation onset. However, mechanisms retaining stem cells in their niche remain poorly understood. Here, we show that the epigenetic regulator lysine-specific demethylase 1 (Lsd1) organises the trophoblast niche of the early mouse embryo by coordinating migration and invasion of trophoblast stem cells (TSCs). Lsd1 deficiency leads to the depletion of the stem cell pool resulting from precocious migration of TSCs.
Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells.
Specimen part, Time
View SamplesThe aim of the study is to identify AR target gens in LNCaP cells Overall design: 6 samples correponding to 2 times 3 replicates were used for the study
Assembly of methylated KDM1A and CHD1 drives androgen receptor-dependent transcription and translocation.
No sample metadata fields
View SamplesPurpose: CEBPA mutations are found as either biallelic (biCEBPA) or monoallelic (moCEBPA). We set out to explore whether the kind of CEBPA mutation is of prognostic relevance in cytogenetically normal AML (CN-AML).
Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome.
Specimen part
View SamplesThe granulosa cells in the mammalian ovarian follicle respond to gonadotropin signalling and are involved in the processes of folliculogenesis and oocyte maturation. Studies on gene expression and regulation in human granulosa cells are of interest due to their potential for estimating the oocyte viability and IVF success. However, the post-transcriptional gene expression studies on miRNA level in the human ovary have been scarce. The current study determined the miRNA profile by deep sequencing of the two intrafollicular somatic cell types: mural and cumulus granulosa cells isolated from women undergoing controlled ovarian stimulation and in vitro fertilization. Overall design: Paired cumulus and mural granulosa samples were analysed from 3 women participating in IVF procedure. Libraries of all 6 samples were sequenced twice, generating 2 technical replicates for each sample. Differential gene expression study was performed on the pooled results of technical replicates.
Research resource: small RNA-seq of human granulosa cells reveals miRNAs in FSHR and aromatase genes.
Specimen part, Subject
View SamplesHTETOP cells, derived from the human fibrosarcoma cell line HT1080, express human topoisomearse II (TOP2A) exclusively from a tetracycline (TET)-regulated transgene, we used HTETOP cells to differentiate between TOP2A-dependent and independent apoptotic effects of doxorubicin and dexrazoxane.
Topoisomerase II{alpha}-dependent and -independent apoptotic effects of dexrazoxane and doxorubicin.
Cell line
View SamplesThe granulosa cells in the mammalian ovarian follicle respond to gonadotropin signalling and are involved in the processes of folliculogenesis and oocyte maturation. Studies on gene expression and regulation in human granulosa cells are of interest due to their potential for estimating the oocyte viability and IVF success. The current study determined the mRNA profile by deep sequencing of the two intrafollicular somatic cell types: mural and cumulus granulosa cells isolated from women undergoing controlled ovarian stimulation and in vitro fertilization. Overall design: Paired cumulus and mural granulosa samples were analysed from 3 women participating in IVF procedure. Differential gene expression study was performed. The identified gene expression profile was also used for predicting targets for miRNAs that were also identified from the same samples (GSE46489).
Research resource: small RNA-seq of human granulosa cells reveals miRNAs in FSHR and aromatase genes.
Specimen part, Subject
View SamplesThe carcinogenic potential of chemicals is currently evaluated with rodent life-time bioassays, which are time consuming, and expensive with respect to cost, number of animals and amount of compound required. Since the results of these 2-year bioassays are not known until quite late during development of new chemical entities, and since the short-term test battery to test for genotoxicity, a characteristic of genotoxic carcinogens, is hampered by low specificity, the identification of early biomarkers for carcinogenicity would be a big step forward. Using gene expression profiles from the livers of rats treated up to 14 days with genotoxic and non-genotoxic carcinogens we previously identified characteristic gene expression profiles for these two groups of carcinogens. We have now added expression profiles from further hepatocarcinogens and from non-carcinogens the latter serving as control profiles. We used these profiles to extract biomarkers discriminating genotoxic from non-genotoxic carcinogens and to calculate classifiers based on the support vector machine (SVM) algorithm. These classifiers then predicted a set of independent validation compound profiles with up to 88% accuracy, depending on the marker gene set. We would like to present this study as proof of the concept that a classification of carcinogens based on short-term studies may be feasible.
Cross-platform toxicogenomics for the prediction of non-genotoxic hepatocarcinogenesis in rat.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cross-platform toxicogenomics for the prediction of non-genotoxic hepatocarcinogenesis in rat.
Sex, Specimen part
View SamplesIn this study we performed microarray-based molecular profiling of liver samples from Wistar rats exposed to genotoxic carcinogens (GC), nongenotoxic carcinogens (NGC) or non-hepatocarcinogens (NC) for up to 14 days. In contrast to previous toxicogenomics studies aimed at the inference of molecular signatures for assessing the potential and mode of compound carcinogenicity, we considered multi-level omics data. Besides evaluating the predictive power of signatures observed on individual biological levels, such as mRNA, miRNA and protein expression, we also introduced novel feature representations which capture putative molecular interactions or pathway alterations by integrating expression profiles across platforms interrogating different biological levels.
Cross-platform toxicogenomics for the prediction of non-genotoxic hepatocarcinogenesis in rat.
Sex, Specimen part
View Samples