CircESRP1 inhibits clear cell renal cell carcinoma progression through the CTCF-mediated positive feedback loop.

Circular RNA (circRNA), a closed continuous loop formed by back-splicing, has been confirmed to be implicated in a variety of human diseases including cancers. However, the underlying molecular mechanism of circRNA regulating the progression of renal cell carcinoma (RCC) remains largely unclear. In the present study, we identified a novel circular RNA, circESRP1, that derived from the ESRP1 gene locus at 8q22.1 exons. Lower expression of circESRP1 was found in clear cell RCC (ccRCC) tissues and cell lines. Besides, circESRP1 expression level showed inversely correlated with the advanced tumor size, TNM stage and distant metastasis of ccRCC. The expression level of circESRP1 exhibited a positive correlation with CTCF protein but negatively correlated with miR-3942 in 79 ccRCC tissues. In vivo experiments, we found that overexpression of circESRP1 effectively repressed xenograft tumor growth and inhibited c-Myc-mediated EMT progression. CircESRP1 acted as a sponge to competitively bind with miR-3942 as confirmed through RNA pull-down, RIP and dual-luciferase reporter assays. Moreover, CTCF, a downstream target of miR-3942, was validated to specifically promote the circESRP1 transcript expression and regulated by circESRP1/miR-3942 pathway to form a positive feedback loop. We also revealed that the circESRP1/miR-3942/CTCF feedback loop regulated the ccRCC cell functions via c-Myc mediated EMT process. This study provides a novel regulatory model of circRNA via forming a positive-feedback loop that perpetuates the circESRP1/miR-3942/CTCF axis, suggesting that this signaling may serve as a novel target for the treatment of ccRCC.

Characteristics and risk differences of different tumor size on localized prostate cancer: A retrospective cohort study in the SEER database.

OBJECTIVE: We aimed to evaluate the role of tumor size in predicting tumor risk for localized prostate cancer (PCa) patients undergoing radical prostatectomy (RP). METHODS: Twenty-five thousand, one hundred twenty-seven men with PCa receiving RP from 2010 to 2015 were extracted from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier plots and multivariable Cox regression analyses were used to illustrate overall survival (OS) according to the tumor size. The tumor size was confirmed by postoperative pathology after RP. RESULTS: Among overall localized PCa, 84.6% were high-risk PCa, 9.2% were intermediate-risk PCa, and 6.2% were low-risk PCa. Multivariate analyses demonstrated that tumor size ≥21 mm was an independent risk predict factor of low-risk PCa (odds ratio [OR]: 11.940; 95% CI, 9.404-15.161; p < 0.001) and intermediate-risk PCa (OR: 1.887; 95% CI, 1.586-2.245; p < 0.001). Tumor sizes ≤5 mm significantly correlated with high-risk PCa (p < 0.001). Tumor size ≤5 mm had the worst OS in overall localized PCa and high-risk PCa (p < 0.001). CONCLUSIONS: In localized PCa, tumor sizes ≥21 mm may help predict low or intermediate-risk PCa, while tumor sizes ≤5 mm might help predict high-risk PCa. In clinical practice, we should be on high alert for patients with tumors size ≤5 mm due to its poor prognosis after RP.

Pinocembrin ameliorates intermittent hypoxia-induced neuroinflammation through BNIP3-dependent mitophagy in a murine model of sleep apnea.

BACKGROUND: Intermittent hypoxia (IH) caused by obstructive sleep apnea (OSA) leads to neuroinflammation. Pinocembrin has been shown to have neuroprotective effects, while the therapeutic functions under IH condition are still unknown. METHODS: An OSA model was established by CIH exposure inside custom-made chambers. C57BL/6 mice were intraperitoneally injected with pinocembrin (40 mg/kg, i.p.) or vehicle (PBS containing 5% povidone; i.p.), and the changes of behavior on mice were detected by the Morris water maze test. Immunohistochemical staining, western blotting, immunofluorescence assays, and immunoprecipitation were used to investigate the association between NLRP3 inflammasome and BNIP3-dependent mitophagy. The mitochondrial morphology and mitophagosomes were detected under a transmission electron microscope. The detrimental effects of IH were tested by annexin V-FITC/PI staining, Mito SOX Red staining, and JC-1 mitochondrial membrane potential assay. RESULTS: In this study, our observations in vivo indicated that the administration of pinocembrin can restore spatial learning and memory ability and reduce neuronal apoptosis and hippocampal inflammation. Pinocembrin treatment significantly inhibited the formation of NLRP3 inflammasome and infiltration of microglia and enhanced BNIP3-mediated mitophagy in the hippocampus of IH mice. Additionally, our in vitro results show that pinocembrin protects microglial cells against IH-induced cytotoxicity by activating BNIP3-dependent mitophagy through the JNK-ERK signaling pathway. CONCLUSIONS: In summary, our findings demonstrated that pinocembrin can act as a potential therapeutic strategy for IH-induced neuroinflammation.

Ratio of prostate specific antigen to the outer gland volume of prostrate as a predictor for prostate cancer.

OBJECTIVE: As a definite diagnosis of prostate cancer, puncture biopsy of the prostate is invasive method. The aim of this study was to evaluate the value of OPSAD (the ratio of PSA to the outer gland volume of prostate) as a non-invasive screening and diagnosis method for prostate cancer in a select population. METHODS: The diagnosis data of 490 subjects undergoing ultrasound-guided biopsy of the prostate were retrospectively analyzed. This included 133 patients with prostate cancer, and 357 patients with benign prostate hyperplasia (BPH). RESULTS: The OPSAD was significantly greater in patients with prostate cancer (1.87 ± 1.26 ng/ml(2)) than those with BPH (0.44 ± 0.21 ng/ml(2)) (P < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the performance of OPSAD as a diagnostic tool is superior to PSA and PSAD for the diagnosis of prostate cancer. In the different groups divided according to the Gleason score of prostate cancer, OPSAD is elevated with the rise of the Gleason score. CONCLUSION: OPSAD may be used as a new indicator for the diagnosis and prognosis of prostate cancer, and it can reduce the use of unnecessary puncture biopsy of the prostate.