MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer

• Published in: Oncotarget 2017-05, Vol.8 (18), p.29540-29557
• Main Authors: Canu, Valeria, Sacconi, Andrea, Lorenzon, Laura, Biagioni, Francesca, Lo Sardo, Federica, Diodoro, Maria Grazia, Muti, Paola, Garofalo, Alfredo, Strano, Sabrina, D'Errico, Antonietta, Grazi, Gian Luca, Cioce, Mario, Blandino, Giovanni
• Format: Article
• Language: English
• Subjects: Bile Duct Neoplasms - genetics; Bile Duct Neoplasms - mortality; Bile Duct Neoplasms - pathology; Cell Cycle - genetics; Cell Line, Tumor; Cell Movement - genetics; Cholangiocarcinoma - genetics; Cholangiocarcinoma - mortality; Cholangiocarcinoma - pathology; Computational Biology - methods; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Ontology; Humans; Male; MicroRNAs - genetics; Neoplasm Grading; Neoplasm Staging; Priority Research Paper; Prognosis; RNA Interference; RNA, Messenger - genetics; Stomach Neoplasms - genetics; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Transcriptome
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.15290

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. 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. 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. We suggest that restoring the physiological levels of miR-204 in some gastrointestinal cancers might be exploited therapeutically.