Project description:Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived tumor xenografts (PDTXs) have been increasingly used as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. Extensive multiomics characterization of these PDTXs have demonstrated their utility as a suitable model for preclinical studies, representing the diversity of the primary cancers. We performed a multi-factorial integrative analysis of genome-wide ChIP-seq on multiple histone modifications, as well as RNA-seq on subcutaneous PDTXs from 24 PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). In the dataset, ChIP-seq for five distinct histone marks (H3K4me1, H3K27ac, H3K4me3, H3K27me3, and H3K9me3) and RNA-seq was carried out to generate new knowledge on the epigenetic landscapes underlying the heterogeneity of PDAC tissues grown in this manner.
Project description:The goal of this study was to determine IGF2BP3 regulation of RNA targets in human pacreatic ductal adenocarcinoma cell lines Included are iCLIP-seq libraries for IGF2BP3 from PL45 and Panc1 PDAC cell samples, RIP-seq samples from PL45 and Panc1 PDAC cells, RNA-seq data sets from control and IGF2BP3 knockdown in PL45 and Panc1 PDAC cells, and small RNA-seq samples from Panc1 cells
Project description:Chromatin remodeling proteins are frequently dysregulated in human cancer, yet little is known about how they control tumorigenesis. Here, we uncover an epigenetic program mediated by the NAD+-dependent histone deacetylase Sirtuin 6 (SIRT6) that is critical for suppression of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies. SIRT6 inactivation accelerates PDAC progression and metastasis via upregulation of Lin28b, a negative regulator of the let-7 microRNA. SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let-7 target genes, HMGA2, IGF2BP1 and IGF2BP3. This epigenetic program defines a distinct subset representing 30-40% of human PDAC, characterized by poor prognosis and an exquisite dependence on Lin28b for tumor growth. Thus, we identify SIRT6 as an important PDAC tumor suppressor, and uncover the Lin28b pathway as a potential therapeutic target in a molecularlydefined PDAC subset. ChIP-Seq experiments to examine H3K56ac histone modifications in murine PDAC cells that are Sirt6 wild type (WT), Sirt6 knock-out (KO), and Sirt6 KO cells engineered to express Sirt6 WT (Sirt6 KO + Sirt6 WT Restored).
Project description:The first GSSM of V. vinifera was reconstructed (MODEL2408120001). Tissue-specific models for stem, leaf, and berry of the Cabernet Sauvignon cultivar were generated from the original model, through the integration of RNA-Seq data. These models have been merged into diel multi-tissue models to study the interactions between tissues at light and dark phases.