MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer
Bibliographic record
Abstract
// Valeria Canu 1,* , Andrea Sacconi 1,* , Laura Lorenzon 2 , Francesca Biagioni 1 , Federica Lo Sardo 1 , Maria Grazia Diodoro 4 , Paola Muti 5 , Alfredo Garofalo 3 , Sabrina Strano 5,6 , Antonietta D’Errico 7 , Gian Luca Grazi 3 , Mario Cioce 1 and Giovanni Blandino 1,5 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 Correspondence to: Giovanni Blandino, email: // Keywords : gastric cancer, cholangiocarcinoma, micro-RNA, miR-204, prognostic Received : September 18, 2016 Accepted : January 27, 2017 Published : February 11, 2017 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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".