Epigenetic silencing of miR-145-5p contributes to brain metastasis
Bibliographic record
Abstract
// Sara Donzelli 1 , Federica Mori 2 , Teresa Bellissimo 1 , Andrea Sacconi 1 , Beatrice Casini 3 , Tania Frixa 1 , Giuseppe Roscilli 4 , Luigi Aurisicchio 4 , Francesco Facciolo 5 , Alfredo Pompili 6 , Maria Antonia Carosi 3 , Edoardo Pescarmona 3 , Oreste Segatto 7 , Greg Pond 8 , Paola Muti 8 , Stefano Telera 6 , Sabrina Strano 2,8 , Yosef Yarden 9 and Giovanni Blandino 1,8 1 Translational Oncogenomics Unit, Italian National Cancer Institute ‘Regina Elena’, Rome, Italy 2 Molecular Chemoprevention Unit, Italian National Cancer Institute ‘Regina Elena’, Rome, Italy 3 Department of Pathology, Italian National Cancer Institute ‘Regina Elena’, Rome, Italy 4 Takis s.r.l., Roma, Italy 5 Unit of Thoracic Surgery, Italian National Cancer Institute ‘Regina Elena’, Rome, Italy 6 Department of Neurosurgery, Italian National Cancer Institute ‘Regina Elena’, Rome, Italy 7 Laboratory of Cell Signaling, Italian National Cancer Institute ‘Regina Elena’, Rome, Italy 8 Department of Oncology, Faculty of Health Science, McMaster University, Hamilton, Canada 9 Weizmann Institute of Science, Department of Biological Regulation, Rehovot, Israel Correspondence to: Giovanni Blandino, email: // Keywords : brain metastases; lung cancer; mir-145-5p; epigenetic modifications; migration Received : June 27, 2015 Accepted : September 14, 2015 Published : September 30, 2015 Abstract Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of several microRNAs, including common down-regulation of miR-145-5p. Down-regulation was attributed to methylation of miR-145’s promoter and affiliated elevation of several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly, tumor protein D52 (TPD52). In line with these observations, restored expression of miR-145-5p and selective depletion of individual targets markedly reduced in vitro and in vivo cancer cell migration. In aggregate, our results attribute to miR-145-5p and its direct targets pivotal roles in malignancy progression and in metastasis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".