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MiRNA expression from gp130F/F mice antrum at 4 weeks of age

ABSTRACT: The molecular events promoting the initiation of gastric cancer (GC), the third most lethal cancer worldwide, are ill-defined. Here, we demonstrate that upregulation of miR-200 family members is associated with tumor initiation in the gp130F/F mouse model of early GC. The onset of gastric inflammation-associated adenomatous hyperplasia in gp130F/F mice occurs at ~6 weeks of age, with established intestinal-type tumors (3 months of age) progressively growing until a maximum size is reached at 6 months of age, with some evidence of carcinoma in situ. Since this phenotype histologically mimics early stage human GC, we therefore utilized gp130F/F mice as a model to identify miRNAs involved in the initiating molecular events leading to early stage GC. For this purpose, we performed miRNA microarrays on mouse gastric antrum tissue from gp130F/F and sex-matched littermate wild-type (gp130+/+) control mice aged 4 weeks; this age was chosen since antrum tissue from 4 week old (wo) gp130F/F mice is devoid of any histological signs of inflammation or hyperplasia, and is thus comparable to wild-type gastric antrum tissue

ORGANISM(S): Mus musculus synthetic construct

PROVIDER: GSE93169 | GEO | 2017/12/01

SECONDARY ACCESSION(S): PRJNA360227

REPOSITORIES: GEO

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Project description:Transcription factor Foxq1 controls mucin gene expression and granule content in mouse stomach surface mucous cells ; Background and Aims: The gastric mucosa provides a stringent epithelial barrier and produces acid and enzymes that initiate digestion. In this regenerating tissue, progenitors differentiate continually into 4 principal specialized cell types, yet underlying mechanisms of differentiation are poorly understood. We identified stomach-restricted expression of the forkhead transcription factor FOXQ1. Methods: We used a combination of genetic, histochemical, ultrastructural and molecular analysis to study gastric cell lineages with respect to FOXQ1. Results: Within the developing and adult gastrointestinal tract, Foxq1 mRNA is restricted to the stomach, expressed prominently in foveolar (pit) cells, the abundant mucin-producing cells that line the mucosal surface, and required for their complete differentiation. Mice carrying Foxq1 coding mutations show virtual absence of mRNA and protein for the backbone of the predominant stomach mucin, MUC5AC. These observations correspond to a paucity of foveolar-cell secretory vesicles and notable loss of stomach but not intestinal mucus. Transcriptional profiling identified a surprisingly restricted set of genes with altered expression in Foxq1 mutant stomachs. MUC5AC is a highly tissue-restricted product that similarly depends on FOXQ1 in its other major site of expression, conjunctival goblet cells. Conclusions: Taken together, these observations imply that promotion of gastric MUC5AC synthesis is a primary, cell-autonomous function of FOXQ1. This study is the first to implicate a transcription factor in terminal differentiation of foveolar cells and begins to define the requirements to assemble highly specialized organelles and cells in the gastric mucosa. DOI: 10.1053/j.gastro.2008.04.019 Experiment Overall Design: RNA from stomach antrum from 2 of each Satin, Beige, and BL6 mice were compared using microarray analysis.

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MiRNA expression from gp130F/F mice antrum at 4 weeks of age

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