Dataset Information

Identification of key transcription factors in caerulein-induced pancreatitis through expression profiling data.

ABSTRACT: The current study aimed to isolate key transcription factors (TFs) in caerulein-induced pancreatitis, and to identify the difference between wild type and Mist1 knockout (KO) mice, in order to elucidate the contribution of Mist1 to pancreatitis. The gene profile of GSE3644 was downloaded from the Gene Expression Omnibus database then analyzed using the t-test. The isolated differentially expressed genes (DEGs) were mapped into a transcriptional regulatory network derived from the Integrated Transcription Factor Platform database and in the network, the interaction pairs involving at least one DEG were screened. Fisher's exact test was used to analyze the functional enrichment of the target genes. A total of 1,555 and 3,057 DEGs were identified in the wild type and Mist1KO mice treated with caerulein, respectively. DEGs screened in Mist1KO mice were predominantly enriched in apoptosis, mitogen-activated protein kinase signaling and other cancer-associated pathways. A total of 188 and 51 TFs associated with pathopoiesis were isolated in Mist1KO and wild type mice, respectively. Out of the top 10 TFs (ranked by P-value), 7 TFs, including S-phase kinase-associated protein 2 (Skp2); minichromosome maintenance complex component 3 (Mcm3); cell division cycle 6 (Cdc6); cyclin B1 (Ccnb1); mutS homolog 6 (Msh6); cyclin A2 (Ccna2); and cyclin B2 (Ccnb2), were expressed in the two types of mouse. These TFs were predominantly involved in phosphorylation, DNA replication, cell division and DNA mismatch repair. In addition, specific TFs, including minichromosome maintenance complex component 7 (Mcm7); lymphoid-specific helicase (Hells); and minichromosome maintenance complex component 6 (Mcm6), that function in the unwinding of DNA were identified to participate in Mist1KO pancreatitis. The DEGs, including Cdc6, Mcm6, Msh6 and Wdr1 are closely associated with the regulation of caerulein-induced pancreatitis. Furthermore, other identified TFs were also involved in this type of regulation.

SUBMITTER: Qi D

PROVIDER: S-EPMC4464163 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Identification of key transcription factors in caerulein-induced pancreatitis through expression profiling data.

Qi Dachuan D Wu Bo B Tong Danian D Pan Ye Y Chen Wei W

Molecular medicine reports 20150512 2

The current study aimed to isolate key transcription factors (TFs) in caerulein-induced pancreatitis, and to identify the difference between wild type and Mist1 knockout (KO) mice, in order to elucidate the contribution of Mist1 to pancreatitis. The gene profile of GSE3644 was downloaded from the Gene Expression Omnibus database then analyzed using the t-test. The isolated differentially expressed genes (DEGs) were mapped into a transcriptional regulatory network derived from the Integrated Tran ...[more]

PMID: 25975747

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Project description:BackgroundThe expression of amino acid transporters is known to vary during acute pancreatitis (AP) except for LAT1 (slc7a5), the expression of which remains stable. LAT1 supports cell growth by importing leucine and thereby stimulates mammalian target of rapamycin (mTOR) activity, a phenomenon often observed in cancer cells. The mechanisms by which LAT1 influences physiological and pathophysiological processes and affects disease progression in the pancreas are not yet known.AimTo evaluate the role of LAT1 in the development of and recovery from AP.MethodsAP was induced with caerulein (cae) injections in female and male mice expressing LAT1 or after its knockout (LAT1 Cre/LoxP). The development of the initial AP injury and its recovery were followed for seven days after cae injections by daily measuring body weight, assessing microscopical tissue architecture, mRNA and protein expression, protein synthesis, and enzyme activity levels, as well as by testing the recruitment of immune cells by FACS and ELISA.ResultsThe initial injury, evaluated by measurements of plasma amylase, lipase, and trypsin activity, as well as the gene expression of dedifferentiation markers, did not differ between the groups. However, early metabolic adaptations that support regeneration at later stages were blunted in LAT1 knockout mice. Especially in females, we observed less mTOR reactivation and dysfunctional autophagy. The later regeneration phase was clearly delayed in female LAT1 knockout mice, which did not regain normal expression of the pancreas-specific differentiation markers recombining binding protein suppressor of hairless-like protein (rbpjl) and basic helix-loop-helix family member A15 (mist1). Amylase mRNA and protein levels remained lower, and, strikingly, female LAT1 knockout mice presented signs of fibrosis lasting until day seven. In contrast, pancreas morphology had returned to normal in wild-type littermates.ConclusionLAT1 supports the regeneration of acinar cells after AP. Female mice lacking LAT1 exhibited more pronounced alterations than male mice, indicating a sexual dimorphism of amino acid metabolism.

Project description:BackgroundLung adenocarcinoma (LUAD) is one of the most common cancers worldwide. The etiology and pathophysiology of LUAD remain unclear. The aim of the present study was to identify the key genes, miRNAs and transcription factors (TFs) associated with the pathogenesis and prognosis of LUAD.MethodsThree gene expression profiles (GSE43458, GSE32863, GSE74706) of LUAD were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by GEO2R.The Gene Ontology (GO) terms, pathways, and protein-protein interactions (PPIs) of these DEGs were analyzed. Bases on DEGs, the miRNAs and TFs were predicted. Furthermore, TF-gene-miRNA co-expression network was constructed to identify key genes, miRNAs and TFs by bioinformatic methods. The expressions and prognostic values of key genes, miRNAs and TFs were carried out through The Cancer Genome Atlas (TCGA) database and Kaplan Meier-plotter (KM) online dataset.ResultsA total of 337 overlapped DEGs (75 upregulated and 262 downregulated) of LUAD were identified from the three GSE datasets. Moreover, 851 miRNAs and 29 TFs were identified to be associated with these DEGs. In total, 10 hub genes, 10 key miRNAs and 10 key TFs were located in the central hub of the TF-gene-miRNA co-expression network, and validated using The Cancer Genome Atlas (TCGA) database. Specifically, seven genes (PHACTR2, MSRB3, GHR, PLSCR4, EPB41L2, NPNT, FBXO32), two miRNAs (hsa-let-7e-5p, hsa-miR-17-5p) and four TFs (STAT6, E2F1, ETS1, JUN) were identified to be associated with prognosis of LUAD, which have significantly different expressions between LUAD and normal lung tissue. Additionally, the miRNA/gene co-expression analysis also revealed that hsa-miR-17-5p and PLSCR4 have a significant negative co-expression relationship (r=?0.33, P=1.67e-14) in LUAD.ConclusionsOur study constructed a regulatory network of TF-gene-miRNA in LUAD, which may provide new insights about the interaction between genes, miRNAs and TFs in the pathogenesis of LUAD, and identify potential biomarkers or therapeutic targets for LUAD.

Dataset Information

Identification of key transcription factors in caerulein-induced pancreatitis through expression profiling data.

Publications

Identification of key transcription factors in caerulein-induced pancreatitis through expression profiling data.

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