Abstract | BACKGROUND AND AIMS: RESULTS:
Gastrin increased miR-222 expression in AGSGR cells, with maximum changes observed at 10 nM G17 for 24 h. Signalling occurred via CCK2R and the PKC and PI3K pathways. miR-222 expression was increased in the serum and gastric corpus mucosa of hypergastrinemic INS-GAS mice and hypergastrinemic patients with autoimmune atrophic gastritis and type 1 gastric NETs; it decreased in patients following treatment with the CCK2R antagonist netazepide ( YF476). Gastrin-induced miR-222 overexpression resulted in reduced expression and cytoplasmic mislocalisation of p27kip1, which in turn caused actin remodelling and increased migration in AGSGR cells. MATERIALS AND METHODS:
miRNA PCR arrays were used to identify changes in miRNA expression following G17 treatment of human gastric adenocarcinoma cells stably transfected with CCK2R (AGSGR). miR-222 was further investigated using primer assays and samples from hypergastrinemic mice and humans. Chemically synthesised mimics and inhibitors were used to assess cellular phenotypical changes associated with miR-222 dysregulation. CONCLUSIONS: These data indicate a novel mechanism contributing to gastrin-associated gastric tumor development. miR-222 may also be a promising biomarker for monitoring gastrin induced premalignant changes in the stomach.
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Authors | Katie A Lloyd, Andrew R Moore, Bryony N Parsons, Adrian O'Hara, Malcolm Boyce, Graham J Dockray, Andrea Varro, D Mark Pritchard |
Journal | Oncotarget
(Oncotarget)
Vol. 7
Issue 29
Pg. 45462-45478
(07 19 2016)
ISSN: 1949-2553 [Electronic] United States |
PMID | 27323780
(Publication Type: Journal Article)
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Chemical References |
- Gastrins
- MIRN222 microRNA, human
- MIRN222 microRNA, mouse
- MicroRNAs
- Cyclin-Dependent Kinase Inhibitor p27
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Topics |
- Adenocarcinoma
(genetics, metabolism, pathology)
- Animals
- Cyclin-Dependent Kinase Inhibitor p27
(biosynthesis, genetics)
- Gastrins
(metabolism)
- Gene Expression Regulation, Neoplastic
(genetics)
- Humans
- Mice
- Mice, Transgenic
- MicroRNAs
(biosynthesis, genetics)
- Neuroendocrine Tumors
(genetics, metabolism, pathology)
- Stomach Neoplasms
(genetics, metabolism, pathology)
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