MiR-34a to enhance the radiosensitivity of 22RV1 and 22RV1-radiation resistance prostate cancer cell lines.
Bibliographic record
Abstract
74 Background: Radiation therapy (RT) is a standard treatment option for men with prostate cancer (PCa), yet men still fail RT at a rate of up to 50%. MicroRNAs (miRNAs) can influence the tumor RT response, and the abundance or lack of specific miRNAs can alter radiosensitivity through alteration of survival pathway signals. We show that altered expression of miR-34a plays an important role in radiosensitivity. Methods: Both clinical and molecular data from TCGA-PRAD cohort were analyzed. MiR-34a expression was also determined in an independent cohort of 30 patients with PCa treated with RT. An RT resistant subline (22RV1-IRR) from the parental 22RV1 line was generated. MiR-34a expression level was determined in 22RV1, 22RV1-IRR and PrEC cells. 22RV1 and 22RV1-IRR cells were transfected with miR-34a mimics. Stable clones overexpressing miR-34a were generated. The influence of miR-34a on cellular proliferation, migration, clonogenic survival and response to RT was measured using standard assays. Results: Analysis of TCGA-PRAD data showed that low levels of miR-34a was associated with biochemical recurrence (BCR). In our cohort of 30 PCa patients treated with RT, miR-34a was consistently under expressed and associated with BCR. MiR-34a was down regulated in 22RV1 cells compared to PrEC cells and further down regulated in 22RV1-IRR cells. 22RV1 - IRR cells expressed lower levels of TP53, but overexpressed cMYC, BIRC5 (survivin) and E2F3. MiR-34a mimics resulted in a decreased expression of survivin at the mRNA and protein level in 22RV1 and 22RV1-IRR cells. MiR-34a expression was unregulated in response to RT in both cell lines. Survivin and E2F3 expression were down regulated in response to RT in both cell lines. MiR-34a mimics suppressed cell proliferation in 22RV1 and 22RV1-IRR cells. MiR-34a mimics also suppressed cellular migration, by the wound healing assay, in both 22RV1 and 22RV1-IRR cells. Stable clones overexpressing miR-34a were associated with increased radiosensitivity via clonogenic survival assay. Conclusions: Together, these data suggest that low expression of miR-34a is associated with BCR and overexpression of miR-34a enhances radiosensitivity by the downregulation of survivin and E2F3.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".