It is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset of them are long noncoding RNAs (lncRNAs). Many lncRNAs show aberrant expression in cancer, and some of them have been linked to cellular transformation. However, the underlying mechanisms remain poorly understood. Here we characterize the function of the p53-regulated human lncRNA LINC-PINT in cancer. We found that LINC-PINT acts as tumor suppressor lncRNA. Its expression is downregulated in multiple types of cancer and correlates with good prognosis in lung adenocarcinoma. LINC-PINT inhibits the migration capacity and invasive phenotype of cancer cells in vitro and in vivo, and it does so by repressing a proinvasion gene signature in a PRC2-dependent manner. By applying cross-species conservation analysis combined with functional experimental validations we found that the function of LINC-PINT is highly dependent on a short sequence conserved across mammals, sequence that mediates the interaction with PRC2. We propose that LINC-PINT may function as a molecular exchanger that provides PRC2 to active gene promoters for their silencing, mechanisms that could be shared by other PRC2-interacting lncRNAs.
The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element.
Specimen part, Cell line
View SamplesThe mRNA processing body is a cellular structure that regulates the stability of cytoplasmic mRNA. MARF1/LMKB is an RNA-binding protein that is associated with maintenance of mRNA homeostasis and genomic stability. To investigate the function of LMKB in a human B lymphocyte cell line, BJAB cells were treated with either control lentivirus or a lentivirus containing LMKB siRNA.
LMKB/MARF1 localizes to mRNA processing bodies, interacts with Ge-1, and regulates IFI44L gene expression.
Specimen part, Cell line
View SamplesAlveolar rhabdomyosarcoma (aRMS) is an aggressive sarcoma of skeletal muscle characterized by expression of the PAX3-FOXO1 fusion gene. Despite its discovery over almost 20 years ago, PAX3-FOXO1 remains an enigmatic tumor driver. Previously, we reported that PAX3-FOXO1 supports aRMS initiation by enabling bypass of cellular senescence. Here, we show that bypass occurs in part by PAX3-FOXO1-mediated upregulation of RASSF4, a Ras-association domain family (RASSF) member, which then suppresses the evolutionarily conserved mammalian Hippo/Mst1 pathway. RASSF4 loss-of-function activates Hippo/Mst1 and inhibits downstream YAP, causing aRMS cell cycle arrest and senescence. This is the first evidence for an oncogenic role for RASSF4, and a novel mechanism for Hippo signaling suppression in human cancer.
Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression.
Cell line, Treatment
View SamplesWe hypothesize that gene expression in the lungs of these differentially-treated mice are divergent thus contributing to the disparity in their phenotypes. More specifically, (1) Effects of Leptin-treatment of ob/ob postnatal mice lungs are known to be volume-dependent from 2 to 10 wks of age, and are independent of the hypometabolism associated with leptin deficiency. ; (2) Leptin is critical to postnatal lung remodeling, particularly related to enlarged alveolar surface area. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between lungs of leptin or saline-treated ob/ob postnatal mice.
Effects of leptin deficiency on postnatal lung development in mice.
No sample metadata fields
View SamplesTranscripomic analysis of leaf gene expression in S and N-deficient winter wheat during grain development. Tissue was harvested at anthesis and 7, 14 and 21 days post anthesis from experimental field plots.
Co-ordinated expression of amino acid metabolism in response to N and S deficiency during wheat grain filling.
Specimen part, Disease, Disease stage, Subject, Time
View SamplesTrisomy 21 (Ts21) or Down syndrome (DS) is the most common genetic cause of intellectual disability. To investigate the consequences of Ts21 on human brain development, we have systematically analyzed the transcriptome of dorsolateral prefrontal cortex (DFC) and cerebellar cortex (CBC) using exon array mapping in DS and matched euploid control brains spanning from prenatal development to adulthood. We identify hundreds of differentially expressed (DEX) genes in the DS brains, many of which exhibit temporal changes in expression over the lifespan. To gain insight into how these DEX genes may cause specific DS phenotypes, we identified functional modules of co-expressed genes using several different bioinformatics approaches, including WGCNA and gene ontology analysis. A module comprised of genes associated with myelination, including those dynamically expressed over the course of oligodendrocyte development, was amongst those with the great levels of differential gene expression. Using Ts65Dn mouse line, the most common rodent model of DS, w e observed significant and novel defects in oligodendrocyte maturation and myelin ultrastructure; establishing a correlative proof-of-principle implicating myelin dysgenesis in DS. Thus, examination of the spatio-temporal transcriptome predicts specific cellular and functional events in the DS brain and is an outstanding resource for determining putative mechanisms involved in the neuropathology of DS.
Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination.
Sex, Disease, Race
View SamplesMutations in GRIN2B are associated with intellectual disability in humans. We generated iPSC derived mature cortical neurons with mutations in GRIN2B and compared them to isogenic control cells. We found that both loss of function (LOF) and reduced dosage (RD) mutations in GRIN2B lead to reduced expression of NMDAR genes and increased expression of marker of immaturity, including KI67 and MET. Overall design: Examination of transcriptome in iPSC-derved mature neurons with and without the presence of mutations in GRIN2B
Disruption of GRIN2B Impairs Differentiation in Human Neurons.
Subject
View SamplesTo probe the tissue source (cancer cell VS stromal cell) of gene expression in the mixed tumor samples, we took advantage of a set of Urothelial Cancer patient-derived xenograft (PDX) models given that the transcriptome in these models is a mixture of human RNA (derived from cancer cells) and mouse RNA (derived from stromal cells). Overall design: The cohort includes 5 different patient-derived PDX models, 3 replicates for each model, and thus a total of 15 samples
EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer.
Subject
View SamplesTo identify novel LXR target genes, we conducted transcriptional profiling studies using RAW264.7 cells ectopically expressing
Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR.
Cell line
View SamplesAutism Spectrum Disorder (ASD) is a common pediatric cognitive disorder with high heritability. Yet no single genetic variant has accounted for more than a small fraction of cases. We sought to determine whether we could classify patients as having ASD vs. controls solely based on a multi-gene expression profiling of their peripheral blood cells.
Characteristics and predictive value of blood transcriptome signature in males with autism spectrum disorders.
Sex, Disease, Race
View Samples