Valeria Canu1, Andrea Sacconi1, Laura Lorenzon2, Francesca Biagioni1, Federica Lo Sardo1, Maria Grazia Diodoro3, Paola Muti4, Alfredo Garofalo5, Sabrina Strano4,6, Antonietta D'Errico7, Gian Luca Grazi5, Mario Cioce1, Giovanni Blandino1,4. 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. Department of Research, Advanced Diagnostic, and Technological Innovation, Regina Elena National Cancer Institute, Rome, Italy. 4. Department of Oncology, Juravinski Cancer Center, McMaster University Hamilton, Hamilton, Ontario, Canada. 5. HepatoBiliary Pancreatic Surgery, 'Regina Elena' National Cancer Institute, Rome, Italy. 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.
Abstract
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.
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.
Authors: F Bernuzzi; F Marabita; A Lleo; M Carbone; M Mirolo; M Marzioni; G Alpini; D Alvaro; K M Boberg; M Locati; G Torzilli; L Rimassa; F Piscaglia; X-S He; C L Bowlus; G-X Yang; M E Gershwin; P Invernizzi Journal: Clin Exp Immunol Date: 2016-05-17 Impact factor: 4.330
Authors: Annika Bergquist; Anders Ekbom; Rolf Olsson; Dan Kornfeldt; Lars Lööf; Ake Danielsson; Rolf Hultcrantz; Stefan Lindgren; Hanne Prytz; Hanna Sandberg-Gertzén; Sven Almer; Fredrik Granath; Ulrika Broomé Journal: J Hepatol Date: 2002-03 Impact factor: 25.083
Authors: Mona El Khatib; Przemyslaw Bozko; Vindhya Palagani; Nisar P Malek; Ludwig Wilkens; Ruben R Plentz Journal: PLoS One Date: 2013-10-30 Impact factor: 3.240
Authors: Yi Chu; Mingzuo Jiang; Feng Du; Di Chen; Tao Ye; Bing Xu; Xiaowei Li; Weijie Wang; Zhaoyan Qiu; Haiming Liu; Yongzhan Nie; Jie Liang; Daiming Fan Journal: FEBS Open Bio Date: 2018-01-15 Impact factor: 2.693