Project description:A 45h time-course RNA-seq study was performed to analyse the different circadian phenotypes of human colorectal cancer cell line HCT116 WT, HCT116 ARNTL Knockout, HCT116 PER2 Knockout and HCT116 NR1D1 Knockout cells. Samples were taken every 3h starting from 9h after cell synchronization for a period of 45h resulting in 16 time-points for each cell line.
Project description:Saliva is considered as the best source for biomarker-discovery studies, since it is a non-invasive method when compared to other body sources. Usually, buffalo cannot express their estrus signs precisely. Hence, there is a need for concise methods to detect the time of estrus to ensure the success in artificial insemination. Therefore, we have established a reference proteome map on buffalo whole saliva during estrous cycle in order to document the estrus-specific proteins using SDS-PAGE and mass spectrometry. The present findings conclude that the proteomic approach adopted to identify the proteins from buffalo saliva around estrous cycle may provide a new tool for screening the estrus phase.
Project description:Lung cancer is the most frequent cancer-related cause of death, and adenocarcinoma (LUAD) is the most frequent type. Despite the recent success of immunotherapies, survival of lung cancer patients has not significantly improved in the last decades. New therapies are necessary. We have previously identified sodium-glucose transporter 2 (SGLT2) as the major responsible for glucose uptake in LUAD, and we have showed that treatment with SGLT2 inhibitors significantly delays LUAD development and prolongs survival in murine models. However, our data shows that SGLT2 inhibitors also induce de-differentiation of LUAD cells, leading to a more aggressive phenotype and increased resistance to cisplatin. Glucose deprivation causes reduced αKG levels, leading to reduced activity of αKG-dependent histone demethylases and consequent histone hypermethylation. Supplementation of αKG or inhibition of the histone methyltransferase EZH2 reverse this phenotype, suggesting that this de-differentiated phenotype depends on insufficiency of αKG-dependent histone demethylases and unbalanced EZH2 activity. Consistently, double treatment with an SGLT2 inhibitor and an EZH2 inhibitor significantly reduces the tumor burden in a genetically engineered murine model of LUAD. We further characterized the effect of low glucose-induced tumor de-differentiation, identifying stabilization of hypoxia inducible factor 1α (HIF1α) as a major pathway responsible for the acquisition of a more aggressive phenotype following glucose deprivation. Finally, we identified an HIF1α-dependent transcriptional signature with prognostic significance in human LUAD. Our studies further our knowledge of the relationship between glucose metabolism and cell differentiation in cancer, characterizing the epigenetic adaptation of cancer cells to nutrient deprivation and identifying novel targets to prevent the development of resistance to metabolic therapies.
Project description:Mesothelial cells, which interact with endothelial cells, are widely used in research including cancer and drug development, have not been comprehensively profiled. We therefore performed RNA sequencing of polarized, primary peritoneal (HPMC) and immortalized pleural mesothelial cells (MeT-5A), and compared it to endothelial cells from umbilical vein (HUVEC) and cardiac capillaries (HCMEC).
Project description:Glioblastoma (GBM) is the most frequent and aggressive form of primary brain tumor in the adult population, and the high recurrence rate and resistance to current therapeutics urgently demand a better therapy for this disease. Regulation of protein stability by the ubiquitin proteasome system (UPS) represents an important control mechanism of cell growth. Deregulation of UPS is mechanistically linked to the development and progression of a variety of human cancers, including GBM. Thus, UPS system represents a valuable target for GBM treatment. Here, we find that the E3 ligase praja2 selectively marks primary IDH1-wild type GBM. By using an integrated approach, including proteomics, transcriptomics and metabolic profiling, we identify praja2 as a main component of a signaling network that regulates cancer cell growth and metabolism. We show that praja2 binds and regulates the stability of the Kinase Suppressor of Ras 2 (KSR2) and as consequence, the activity of the downstream AMP-dependent protein kinase (AMPK) in GBM cells. By degrading KSR2, praja2 attenuates the oxidative metabolism and promotes the aerobic glycolysis (Warburg effect). Brain delivery of siRNAs targeting praja2 upregulates KSR2 and negatively impacted on GBM growth, reducing the tumor size and significantly improving the survival rate of treated mice. These data highlight the role of praja2 as an essential regulator of cancer cell metabolism, and as a preferential therapeutic target to suppress GBM growth
Project description:RNA Seq data showed 49 differentially altered mRNAs in estrus and diestrus stages of buffalo cell free saliva, that includes 10 mRNAs commonly present in both estrus and diestrus stages, whereas 12 and 27 mRNAs were found to be exclusively present either at the estrus or the diestrus stage respectively. In addition, four mature miRNAs were predicted to be differentially altered in the estrus as compared to the diestrus phase of buffaloes.
Project description:As part of cross-platform comparisons of microarray and RNA-seq, this current experiment using the Affymetrix Human Transcriptome Array 2.0 aimed to quantify gene-level expression in subjects administered recombinant human erythropoietin over a 10-week protocol for the identification of gene signatures of blood doping. These results were compared to results obtained from other gene expression quantification platforms using the same experimental cohort, including the Illumina HumanHT-12v4 Expression BeadChips (archived in ArrayExpression; E-MTAB-2874), Illumina NextSeq 500 and MGI DNBSEQ-G400RS.
Project description:We analyzed the effect of knockdown of miR-214 compared to wild type on the expression of genes and pathways involved in prostate cancer cells.
Project description:Upon virus infections, the transcriptomic profile of host plants markedly changes. The rapid and comprehensive transcriptional reprogramming is critical to ward off virus attack. To learn more about transcriptional reprogramming in tobamovirus-infected pepper leaves, we carried out transcriptome-wide RNA-Seq analyses of pepper leaves following Obuda pepper virus (ObPV) and Pepper mild mottle virus (PMMoV)-inoculations.