This study focuses on the effect of miR-129-5p on docetaxel-resistant (DR) prostate cancer (PCa) cells invasion, migration and apoptosis. In our study, the expression of CAMK2N1 was assessed by qRT-PCR in PCa patient tissues and cell lines including PC-3 and PC-3-DR. Cells transfected with miR-129-5p mimics, inhibitor, CAMK2N1 or negative controls (NC) were used to interrogate their effects on DR cell invasions, migrations and apoptosis during docetaxel (DTX) treatments. The apoptosis rate of the PCa cells was validated by flow cytometry. Relationships between miR-129-5pand CAMK2N1 levels were identified by qRT-PCR and dual-luciferase reporter assay.CAMK2N1 was found to be down-expressed in DR PCa tissue sample, and low levels of CAMK2N1 were correlated with high docetaxel resistance and clinical prediction of poor survival. CAMK2N1 levels were decreased in DR PCa cells treated with DXT. We further explored that up-regulation of miR-129-5p could promote DR PCa cells viability, invasion and migration but demote apoptosis. Involved molecular mechanism studies revealed that miR-129-5p reduced downstream CAMK2N1 expression to further impact on chemoresistance to docetaxel of PCa cells, indicating its vital role in PCa docetaxel resistance. Our findings revealed that miR-129-5p contributed to the resistance of PC-3-DR cells to docetaxel through suppressing CAMK2N1 expression, and thus targeting miR-129-5p may provide a novel therapeutic approach in sensitizing PCa to future docetaxel treatment.
Background: Bacillus Calmette–Guérin (BCG) immunotherapy plays a key role in patients with bladder cancer. The shortage of intravesical BCG has motivated researchers to seek alternatives with equivalent efficacy If other alternative intravesical agents have equivalent efficacy compared to BCG, then it may be feasible to replace standard BCG with alternative options. Methods: We searched all relevant evidence in multiple sources and key data was extracted from included studies. Conventional and network meta-analysis were conducted so that pooled odds ratios (ORs) for the event of tumor recurrence and progression can be computed. The relative efficacy of different intravesical instillation procedures was computed by pooled odds ratios and their 95% confidence or creditable intervals. Besides, several key model assumptions were evaluated in our analysis. Results: Three intravesical instillation procedures have the potential for preventing tumor recurrence: standard-dose BCG (BCG_SD), Epirubicin (EPI) and Mitomycin C (MMC) (ORs < 1). Patients with BCG SD also exhibited a decreased risk of tumor recurrence and progression compared to those with EPI. No significant difference in the risk of tumor recurrence or progression was detected between patients treated with BCG_ SD and those with low-dose BCG (BCG_LD). Results of SUCRA indicated that BCG_EPI, BCG_ MMC and BCG SD had higher rankings with respect to tumor recurrence and progression. Conclusions: BCG SD, EPI and MMC exhibited established efficacy for preventing tumor recurrence in postoperative BC patients. The efficacy of BCG may not be significantly reduced if standard dose was reduced to a lower level. However, there is no consensus suggesting that intravesical BCG with standard dose can be replaced by alternating or sequentially combined intravesical instillation therapies.
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