Microrna-198: A novel tumor suppressor in prostate cancer.
Bibliographic record
Abstract
92 Background: microRNAs (miRNAs) are small non-coding RNA molecules which act as repressors of gene function, and have been identified as playing substantial roles in cancer as both tumor suppressors and oncogenes. miR-198 has been reported to be down-regulated in several cancers, with low expression associated with worse overall survival. In addition, miR-198 has demonstrated tumor suppressor effects by altering several hallmarks of cancer. Despite compelling evidence in other cancers, miR-198's role in prostate cancer aggression has not yet been evaluated. Methods: Experiments were conducted by overexpressing miR-198 in three prostate cancer cell lines: DU145, LNCaP and 22RV1. To examine miR-198's effect on hallmarks of cancer in vitro, we used standard protocols to assay proliferation, colony formation, cell cycle profile, migration, and invasive potential. Gene array, qPCR, western blotting, and siRNA knockdown experiments were used to establish miR-198 downstream targets. Results: Overexpression of the candidate tumor suppressor miR-198 diminished proliferation in all prostate cancer cell lines and significantly impaired colony formation in soft agar. Subsequently, miR-198 expression was also demonstrated to reduce growth and tumor formation in vivo using LNCaP xenografts. Gene arrays and in silico target prediction identified several candidate targets, none of which have been previously linked to miR-198. MIB1, an E3 ubiquitin ligase, was the only target we have since identified to be reduced with miR-198 overexpression at both the RNA and protein levels. Knockdown of MIB1 recapitulated miR-198's effects on proliferation and colony formation, and further experiments are underway to demonstrate a direct binding relationship. An additional gene array with MIB1 siRNA will be performed to highlight pathways through which MIB1/miR-198 suppress tumorigenesis. Conclusions: Our evidence supports miR-198 as an important tumor suppressor in prostate cancer, with elevated expression impairing proliferation, colony formation, and in vivo tumor formation. This investigation into miR-198 highlights a potential role as a prostate cancer biomarker, or as a potential target of therapeutics to restore miRNA activity.
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 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 | 0.000 |
| 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) | 0.001 | 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".