Journal
ONCOTARGET
Volume 8, Issue 18, Pages 29540-29557Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15290
Keywords
gastric cancer; cholangiocarcinoma; micro-RNA; miR-204; prognostic
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Funding
- AIRCS (Associazione Italiana Ricerca sulla Colangite Sclerosante)
- AIRC
- Marie Curie Actions - People -COFUND fellowship
- AIRC [N 14455]
- EPIGEN [13/05/R42]
- ArceloMittal Dofasco funding
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Background & Aims: There is high need of novel diagnostic and prognostic tools for tumors of the digestive system, such as gastric cancer and cholangiocarcinoma. We recently found that miR-204 was deeply downregulated in gastric cancer tissues. Here we investigated whether this was common to other tumors of the digestive system and whether this elicited a miR-204-dependent gene target signature, diagnostically and therapeutically relevant. Finally, we assessed the contribution of the identified target genes to the cell cycle progression and clonogenicity of gastric cancer and cholangiocarcinoma cell lines. Methods: We employed quantitative PCR and Affymetrix profiling for gene expression studies. In silico analysis aided us to identifying a miR-204 target signature in publicly available databases (TGCA). We employed transient transfection experiments, clonogenic assays and cell cycle profiling to evaluate the biological consequences of miR-204 perturbation. Results: We identified a novel miR-204 gene target signature perturbed in gastric cancer and in cholangiocarcinoma specimens. We validated its prognostic relevance and mechanistically addressed its biological relevance in GC and CC cell lines. Conclusions: We suggest that restoring the physiological levels of miR-204 in some gastrointestinal cancers might be exploited therapeutically.
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