Contribution of microRNA-200b-3p to radiation therapy resistance in 22RV1 prostate cancer cells.
Bibliographic record
Abstract
89 Background: Radiation therapy (RT) is a standard treatment option for men with localized prostate cancer. Despite having well-established treatment regimens, such men still fail RT at a rate of up to 30-50%. RT resistant phenotype is a key component leading to treatment failure. MicroRNAs (miRNAs) can influence the response to RT, and the abundance or lack of certain miRNAs can induce a RT resistant phenotype through alteration of survival pathways. We show that altered expression of miR-200b-3p plays an important role in contributing to RT resistance. Methods: RT resistant subline from the parental 22RV1 prostate cancer cell line was generated by exposure to fractionated RT – 22RV1-RT. The global expression level of miRNAs and mRNA was determined, using the Affymetrix GeneChip®: miRNA 4.0 and Human Gene 2.0 ST Arrays. Parental and 22RV1-RT cells were transfected with miR-200b-3p mimics or negative control. The influence of miR-200b-3p on cellular proliferation, morphology, migration, clonogenic survival and response to RT was determined by standard assays. Results: MiR-200b-3p was the only miRNA that was statistically differentially expressed between the two cell lines. There were 39 differentially expressed genes. Of the 65 genes predicted to be regulated by miR-200b-3p as identified from miRTarBase, only Fibronectin 1 (FN1) was in common. FN1 was up-regulated in 22RV1- RT cells. MiR-200b-3p mimics; in comparison to negative control mimics, suppressed cell proliferation in both cell lines. Both cell lines with negative control mimics have fibroblastic-type morphology and display a stretched shape following RT. While, cells transfected with miR-200b-3p mimics demonstrated a round morphology and formed clusters following RT. Over-expression of miR-200b-3p mimics inhibited cell migration synergically with RT and demonstrated a lower degree of clonogenic survival following RT in 22RV1-RT cells compared to negative control mimics. Surprisingly, miR-200b-3p mimics reversed the observed RT resistance and the sensitivity to RT was to the same degree as the parental 22RV1 cells. Conclusions: Together, these data suggest that miR-200b-3p independently contributes to RT resistance in 22RV1 prostate cancer cells.
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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 | 0.000 |
| 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".