We profiled the global gene expression of human primary fetal lung fibroblasts (HFL-1) at different stages while they were undergoing replicative senescence
Bioinformatic framework for analysis of transcription factor changes as the molecular link between replicative cellular senescence signaling pathways and carcinogenesis.
Cell line
View SamplesMastic oil from Pistacia lentiscus variation chia, a blend of bioactive terpenes with recognized medicinal properties, has been recently shown to exert anti-tumor activity. Lewis lung carcinoma (LLC) cells are mastic oil-susceptible cells and were used in this work to study the effects of mastic oil at the transcriptomic level.
A transcriptomic computational analysis of mastic oil-treated Lewis lung carcinomas reveals molecular mechanisms targeting tumor cell growth and survival.
Cell line
View SamplesHuman Umbilical Vein Endothelial Cells were treated with three newly synthesized compounds and DMSO as vehicle. Total RNA was isolated 6 and 24h after treatment and gene expression analysis was performed. Three independent experiments were performed, corresponding to rep1, rep2 and rep3. Experiment 1 (rep1) contained all substances at both time points tested. Experiment 2 (rep2) contained two of the compounds and control DMSO at both time points. Experiment 3 (rep3) contained the third compound and control DMSO at both time points.
Novel pyrazolopyridine derivatives as potential angiogenesis inhibitors: Synthesis, biological evaluation and transcriptome-based mechanistic analysis.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Radiogenomic Analysis of F-18-Fluorodeoxyglucose Positron Emission Tomography and Gene Expression Data Elucidates the Epidemiological Complexity of Colorectal Cancer Landscape.
Specimen part
View SamplesColorectal cancer is a highly heterogeneous disease, with variable molecular pathogenesis, involving multiple genomic and epigenetic alterations. Despite the significant advances in the diagnosis and treatment of colorectal cancer, it remains a major cause of morbidity and mortality, especially for countries in Northern America and Europe, as also in New Zealand & Australia. In this direction, the introduction of gene expression signatures derived from multiple layers of molecular & clinical dissection, may resolve the problems of heterogeneity and improve robust disease stratification
Radiogenomic Analysis of F-18-Fluorodeoxyglucose Positron Emission Tomography and Gene Expression Data Elucidates the Epidemiological Complexity of Colorectal Cancer Landscape.
Specimen part
View SamplesColorectal cancer is a highly heterogeneous disease, with variable molecular pathogenesis, involving multiple genomic and epigenetic alterations. Despite the significant advances in the diagnosis and treatment of colorectal cancer, it remains a major cause of morbidity and mortality, especially for countries in Northern America and Europe, as also in New Zealand & Australia. In this direction, the introduction of gene expression signatures derived from multiple layers of molecular & clinical dissection, may resolve the problems of heterogeneity and improve robust disease stratification.
Radiogenomic Analysis of F-18-Fluorodeoxyglucose Positron Emission Tomography and Gene Expression Data Elucidates the Epidemiological Complexity of Colorectal Cancer Landscape.
Specimen part
View SamplesThe study demontrates differences in the transcriptome ( both of protein coding transcripts and long non-coding RNAs) in the unilateral ureteric obstruction model of renal fibrosis. Overall design: Renal tissue was studied from animals undergoing sham operation (as controls) or right ureteric ligation. Animals were sacrificed 2 and 8 days following ligation and the right kidney tissue was examined.
Whole-transcriptome analysis of UUO mouse model of renal fibrosis reveals new molecular players in kidney diseases.
Sex, Age, Specimen part, Cell line, Subject
View SamplesGlioblastoma multiforme is the most lethal form of glioma with an overall survival at 5 years nearly null, which mainly results from acquired resistance to therapies. Large scale sequencing studies on human cancer biopsies defined IRE1alpha as the fifth most oncogenic mutated kinase in human cancer. IRE1alpha is a major component of the Unfolded Protein Response signaling and increasing evidence suggests that it is a central player in GBM development.
Dual IRE1 RNase functions dictate glioblastoma development.
Specimen part, Cell line
View SamplesThe basic helix-loop-helix (bHLH) transcription factor hairy and enhancer of split (Hes3) is a member of the Hes/Hey gene family that regulates developmental processes in progenitor cells from various tissues. We demonstrated the Hes3 expression in mouse pancreatic tissue, suggesting it may have a role in modulating beta-cell function. We employed a transfection approach to address specific functions of Hes3. Hes3 RNA interference opposed the growth of the mouse insulinoma cell line Min6. Western blotting and PCR approaches specifically showed that Hes3 RNA interference opposes the expression of Pdx1 and insulin. Likewise, Hes3 knock down reduced evoked insulin release from Min6 cells.
Hes3 is expressed in the adult pancreatic islet and regulates gene expression, cell growth, and insulin release.
Specimen part
View SamplesScreening small molecules and drugs for activity to modulate alternative splicing, we found that amiloride, distinct from four other intracellular pH-affecting analogues, could normalize the splicing of BCL-X, HIPK3 and RON/MISTR1 transcripts in human hepatocellular carcinoma Huh-7 cells. To elucidate the underlying mechanisms, our proteomic analyses of amiloride-treated cells detected hypo-phosphorylation of splicing factor SF2/ASF and also decreased levels of SRp20 and two un-identified SR proteins. We further observed decreased phosphorylation of AKT, ERK1/2 and PP1, while increased phosphorylation of p38 and JNK, suggesting that amiloride treatment down-regulated kinases and up-regulated phosphatases in the signal pathways known to affect the splicing factor protein phosphorylation. The amiloride effects of splicing factor protein hypo-phosphorylation andnormalizedoncogenic RNA splicing were both abrogated by pre-treatment with a PP1 inhibitor. We then performed global exon array analysis of Huh-7 cells treated with amiloride for 24 hours. Using gene array chips (Affymetrix GeneChip Human Exon 1.0 ST Array of >518000 exons of 42974 genes) for exon array analysis (set parameters of correlation coefficient 0.7, splicing index -1.585 , and log2 ratio -1.585), we found that amiloride influenced the splicing patterns of 551 genes involving at least 584 exons, which included 495 known protein-coding genes involving 526 exons, many of which play key roles in functional networks of ion transport, extracellular matrix, cytoskeletons and genome maintenance. Cellular functional analyses revealed subsequent invasion and migration defects, cell cycle disruption, cytokinesis impairment, and lethal DNA degradation in amiloride-treated Huh-7 cells. This study thus provides mechanistic underpinnings for exploiting small molecule modulation of abnormal RNA splicing for cancer therapeutics.
Small molecule amiloride modulates oncogenic RNA alternative splicing to devitalize human cancer cells.
Cell line
View Samples