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MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer
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Valeria Canu1,*, Andrea Sacconi1,*, Laura Lorenzon2, Francesca Biagioni1, Federica Lo Sardo1, Maria Grazia Diodoro4, Paola Muti5, Alfredo Garofalo3, Sabrina Strano5,6, Antonietta D’Errico7, Gian Luca Grazi3, Mario Cioce1 and Giovanni Blandino1,5
1 Oncogenomic and Epigenetic Unit, Italian National Cancer Institute ‘Regina Elena’, Rome, Italy
2 Faculty of Medicine and Psychology, Surgical and Medical Department of Clinical Sciences, Biomedical Technologies and Translational Medicine, University of Rome ‘La Sapienza’, Sant’Andrea Hospital, Rome, Italy
3 HepatoBiliary Pancreatic Surgery, ‘Regina Elena’ National Cancer Institute, Rome, Italy
4 Department of Research, Advanced Diagnostic, and Technological Innovation, Regina Elena National Cancer Institute, Rome, Italy
5 Department of Oncology, Juravinski Cancer Center, McMaster University Hamilton, Hamilton, Ontario, Canada
6 Molecular Chemoprevention Group, Italian National Cancer Institute ‘Regina Elena’, Rome, Italy
7 Department of Medical and Surgical Sciences, Pathology Unit, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Bologna, Italy
* These authors have equally contributed to this work
Giovanni Blandino, email:
Keywords: gastric cancer, cholangiocarcinoma, micro-RNA, miR-204, prognostic
Received: September 18, 2016 Accepted: January 27, 2017 Published: February 11, 2017
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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