miR-26a-5p restoration via EZH2 silencing blocks the IL-6/STAT3 axis to repress the growth of prostate cancer.

BACKGROUND: Interleukin-6 (IL-6) is involved in the activation of several oncogenic pathways in prostate cancer. However, its upstream trans-signaling pathway remains largely unknown. This work proposes a mechanistic explanation of IL-6's upstream effectors in prostate carcinogenesis. RESEARCH DESIGN & METHODS: Samples were harvested to validate the expression of EZH2, miR-26a-5p, and IL-6. Moreover, the protein and its phosphorylation of STAT3 (signal transducer and transcription activator 3) were assessed in prostate cancer cells. We explored the effects of these effectors on malignant phenotypes in vitro and tumor growth in vivo using functional assays. Bioinformatics analysis, dual-luciferase reporter gene assays, and chromatin immunoprecipitation (ChIP) assays were used to determine their binding relationships. RESULTS: Overexpression of EZH2 and IL-6, and under expression of miR-26a-5p was observed in prostate cancer. Silencing IL-6 repressed STAT3 to suppress the malignant phenotypes of prostate cancer cells. Mechanistically, EZH2 inhibited miR-26a-5p expression by promoting H3K27 histone methylation, and miR-26a-5p restricted the malignant phenotypes of prostate cancer by targeting IL-6. Ectopic EZH2 expression reduced xenograft growth by inhibiting miR-26a-5p and activating the IL-6/STAT3 axis. CONCLUSION: EZH2 May potentially be involved in regulating its expression by recruiting H3K27me3 to the miR-26a-5p promoter region, which could further impact the IL6/STAT3 pathway.

Retrospective analysis of 1470-/980-nm dual-wavelength laser en bloc resection versus transurethral resection of bladder tumor for primary non-muscle-invasive bladder cancer.

To compare the safety and efficacy of en bloc resection of non-muscle-invasive bladder cancer (NMIBC) using a 1470-/980-nm dual-wavelength laser (DwLRBT) compared to the gold standard, transurethral resection (TURBT). The study group included 251 patients with a confirmed diagnosis of NMIBC, 97 in the DwLRBT group and 154 in the TURBT group. Clinical characteristics, complications, and recurrence-free survival were compared between the two groups. There were no differences between the two groups with regard to age, sex, mean tumor size, mean tumor number, tumor location, risk, fever, and reoperation. Compared to TURBT, DwLRBT was associated with a shorter hospitalization time (mean±standard deviation: 5.81±1.48 days vs. 4.96±1.32, respectively, p=0.001), shorter catheterization time (4.98±1.47 vs. 4.20±1.48 days, respectively; p=0.035), and smaller volume of intraoperative bleeding (8.43±6.21 ml vs. 6.15±5.08, respectively; p=0.003). Recurrence-free survival (RFS) was better for DwLRBT than TURBT in the overall cohort (hazard ratio [HR], 0.4323; 95% confidence interval [CI], 0.2852-0.6554; p=0.0004) and for the following subgroups and tumor types: intermediate-risk (HR, 0.2654; 95%CI, 0.1020-0.6904; p=0.0245) and high-risk (HR, 0.4461; 95% CI, 0.2778-0.7162; p=0.0027) groups; and for pedunculate bladder tumors (HR, 0.4158; 95%CI, 0.2401-0.7202; p=0.0063), single bladder tumors (HR, 0.4136; 95%CI, 0.2376-0.7293; p=0.0072), and multiple bladder tumors (HR, 0.2727; 95%CI, 0.1408-0.5282; p=0.0014). DwLRBT is associated with better operative and postoperative outcomes, including, importantly, a longer RFS, compared to TURBT.

MicroRNA-205 suppresses the growth of adrenocortical carcinoma SW-13 cells via targeting Bcl-2.

Compared to adrenocortical adenoma (ACA), adrenocortical carcinoma (ACC) has very poor prognosis and limited treatment options. Also conventional methods to distinguish ACC from ACA can be difficult. At this time, no molecular pathological markers are reliable enough to distinguish either tumor. Recently, increasing data have indicated miRNAs to be crucial regulators in the tumor­related processes. In the present study, we found that miR-205 expression is significantly suppressed in ACC tissues compared with ACAs, and that this induces apoptosis and impairs proliferation of ACC SW-13 cells in vitro as well as inhibits tumor growth in vivo. Using bioinformatic predictions, Bcl-2 was identified to be a target of miR-205 via 3'-untranslated region (3'UTR) interactions, which was confirmed by luciferase assay, qRT-PCR, immunohistochemical assay and western blotting showing that mRNA and protein expression of Bcl-2 were negatively related to miR-205. Further investigation into the mechanism found that activation of Bcl-2 cleaved Bax, releasing caspase-9 and -3 that are involved in the intrinsic apoptosis pathway, eventually inducing SW-13 cell apoptosis. In conclusion, miR-205 suppresses the growth of ACC SW-13 cells via targeting the anti-apoptotic gene Bcl-2.