A novel circular RNA, circMAML3, promotes tumor progression of prostate cancer by regulating miR-665/MAPK8IP2 axis.

Many studies have now demonstrated that circRNAs are aberrantly expressed in cancer and are involved in the regulation of malignant tumor progression. However, the role of circMAML3 (hsa_circ_0125392) in prostate cancer has not been reported. circMAML3 was selected from public data through screening. The circMAML3 circular characterization was performed using Sanger sequencing, agarose gel electrophoresis assay, RNase R assay and actinomycin D assay. The expression of circMAML3 in prostate cancer tissues and cells was detected by qRT-PCR. In vivo and in vitro experiments were conducted to investigate the biological functions of circMAML3 in prostate cancer. Finally, the underlying mechanism of circMAML3 was revealed by qRT-PCR, luciferase reporter assay, miRNA Pulldown, RNA immunoprecipitation, western blotting, and rescue assay. Compared to normal prostate tissue and prostate epithelial cells, circMAML3 is highly expressed in prostate cancer tissues and cell lines. CircMAML3 overexpression promotes prostate cancer proliferation and metastasis, while knockdown of circMAML3 exerts the opposite effect. Mechanistically, circMAML3 promotes prostate cancer progression by upregulating MAPK8IP2 expression through sponge miR-665. Our research indicates that circMAML3 promotes prostate cancer progression through the circMAML3/miR-665/MAPK8IP2 axis. circMAML3 and MAPK8IP2 are upregulated in prostate cancer expression and play an oncogenic role, whereas miR-665 is downregulated in prostate cancer and plays an oncogenic role. Therefore, CircMAML3 may be a potential biomarker for prostate cancer diagnosis, treatment and prognosis.

The slope associated with nadir prostate-specific antigen is prognostically significant in men with hormone-sensitive prostate cancer after primary androgen deprivation therapy.

BACKGROUND: Prognostic indicators based on the initial prostate-specific antigen (PSA) levels, nadir PSA, and time to PSA nadir were calculated to evaluate prognosis after primary androgen deprivation therapy (PADT), as these have been reported in very few studies. We attempted to evaluate the prognostic role of the slope associated with nadir PSA in patients treated with PADT. METHODS: A total of 107 patients who were treated with PADT from 2015 to 2019 were reviewed. The Kaplan-Meier method and Cox regression model were used to analyze the prognostic significance of the slope associated with nadir PSA in predicting progression-free survival (PFS) and overall survival (OS). RESULTS: After PADT, the median follow-up duration was 40.1 months; 66 patients (61.7%) had disease progression, and 33 patients (30.8%) died. In the univariate analysis, T stage, N stage, nadir PSA, time to PSA nadir, nadir PSA declining slope (nPSA-DS), nadir PSA percentage declining slope (nPSA-PDS), and nadir PSA line slope (nPSA-LS) were significant predictors for PFS and OS. The multivariate analysis showed that a higher nPSA-DS (> - 0.74) and lower PSA nadir (≤0.16 ng/ml) were independent predictors for prolonged survival. The significance of nPSA-DS and nPSA was supported by the analysis of nPSA-DS and nPSA as time-dependent covariates. The combined analyses demonstrated that patients with a higher nPSA-DS and lower PSA nadir had the best PFS and OS. CONCLUSIONS: The slope associated with the nadir PSA of nPSA-DS was a significant independent predictor for patients treated with PADT. Nadir PSA and nPSA-DS have a synergistic effect on prognosis.