Large scale transcriptome sequencing efforts have vastly expanded the catalog of long non-coding RNAs (lncRNAs) with varying evolutionary conservation, lineage expression, and cancer specificity. Here we functionally characterize a novel ultraconserved lncRNA, THOR (ENSG00000226856), which exhibits expression exclusively in testis and a broad range of human cancers. THOR knockdown and overexpression in multiple cell lines and animal models alters cell or tumor growth supporting an oncogenic role. We discovered a conserved interaction of THOR with IGF2BP1 and show that THOR contributes to the mRNA stabilization activities of IGF2BP1. Notably, transgenic THOR knockout produced fertilization defects in zebrafish and also conferred a resistance to melanoma onset. Likewise, ectopic expression of human THOR in zebrafish accelerated the onset of melanoma. THOR represents a novel class of functionally important cancer/testis lncRNAs whose structure and function have undergone positive evolutionary selection.
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Histone methyltransferase MLL3 contributes to genome-scale circadian transcription.
Specimen part, Time
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Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes.
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View SamplesPrimary cell cultures were isolated from KrasG12D-driven, PiggyBac transposon-transposase pancreatic cancer cell cultures and subjected to microarray-based expression profiling for the investigation of expression profiles.
Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes.
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View SamplesTranscriptome seqeunecing on 16 paired HCCs and non-tumorous livers to investigate the effect of HBV integration
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View Samplesold and young human cardiac fibroblasts plus those treated with rapamycin and methionine restriction or a combination of both
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Sex, Specimen part
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View SamplesPTEN encodes a lipid phosphatase that is underexpressed in many cancers owing to deletions, mutations or gene silencing. PTEN dephosphorylates phosphatidylinositol 3,4,5-triphosphate (PIP3), thereby opposing the activity of class I phosphatidylinositol 3-kinases (PI3Ks) that mediate growth and survival factors signaling through PI3K effectors such as AKT and mTOR. To determine whether continued PTEN inactivation is required to maintain malignancy, we generated an RNAi-based transgenic mouse model that allows tetracycline-dependent regulation of PTEN in a time- and tissue-specific manner. Postnatal PTEN knockdown in the hematopoietic compartment produced highly disseminated T-cell leukemia (T-ALL). Surprisingly, reactivation of PTEN mainly reduced T-ALL dissemination but had little effect on tumor load in hematopoietic organs. Lymphoma infiltration into the intestine was dependent on CCR9 G-protein coupled receptor (GPCR) signaling, which was amplified by PTEN loss. Our results suggest that in the absence of PTEN, GPCRs may play an unanticipated role in driving tumor growth and invasion in an unsupportive environment. They further reveal that the role of PTEN loss in tumor maintenance is not invariant and can be influenced by the tissue microenvironment, thereby producing a form of intratumoral heterogeneity that is independent of cancer genotype.
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View SamplesObesity, an immense epidemic affecting approximately half a billion adults, has doubled in prevalence in the last several decades. Epidemiological data support that obesity due to intake of a high-fat, western diet increases the risk of colon cancer; however, the mechanisms underlying this risk remain unclear. Here, utilizing next generation RNA sequencing, we aimed to determine the high-fat diet mediated gene expression profile in mouse colon and the AOM/DSS model of colon cancer.
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Sex, Specimen part, Disease, Cell line, Treatment
View SamplesHOX A13 over expression represents: i) a novel molecular marker of hepatocellular carcinomas; ii) a sign of epithelial-endothelial transition accounting for tumor independent angiogenesis and lymphangiogenesis.
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