Prostate cancer (PCa) is a common malignant tumor with high morbidity and mortality worldwide. The prostate cancer stem cell (PCSC) model provides novel insights into the pathogenesis of PCa and its therapeutic response. However, the roles and molecular mechanisms of specific genes in mediating fate decisions of PCSCs and carcinogenesis of PCa remain to be elusive. In this study, we have explored the expression, function, and mechanism of AZGP1P2, a pseudogene of AZGP1, in regulating the stemness and apoptosis of PCSCs and treatment resistance of docetaxel in castration-resistant prostate cancer (CRPC). We revealed that AZGP1P2 was downregulated in CRPC cell lines and PCSCs, while it was positively associated with progression-free interval. Upregulation of the AZGP1P2 enhanced the sensitivity of docetaxel treatment in CRPCs via inhibiting their stemness. RNA pull-down associated with mass spectrometry analysis, co-immunoprecipitation assay, and RNA immunoprecipitation assay demonstrated that AZGP1P2 could bind to UBA1 and RBM15 as a “writer” of methyltransferase to form a compound. UBA1, an E1 ubiquitin-activating enzyme, contributed to RBM15 protein degradation via ubiquitination modification. Methylated RNA immunoprecipitation assay displayed that RBM15 controlled the mRNA decay of TPM1 in m6A methylation. Furthermore, a xenograft mouse model and patient-derived organoids showed that the therapeutic effect of docetaxel in CRPC was increased by AZGP1P2 in vivo. Collectively, these results imply that AZGP1P2 mediates the stemness and apoptosis of PCSCs and promotes docetaxel therapeutic effect by suppressing tumor growth and metastasis via UBA1/RBM15-mediated TPM1 mRNA decay in CRPC.

Autologous endothelial progenitor cells (EPCs) might be alternative angiogenic cell sources for vascularization of tissue-engineered bladder, while isolation and culture of EPCs from peripheral blood in adult are usually time-consuming and highly inefficient. Recent evidence has shown that EPCs also exist in the adipose tissue. As adipose tissue is plentiful in the human body and can be easily harvested through a minimally invasive method, the aim of this study was to culture and characterize EPCs from adipose tissue (ADEPCs) and investigate their potential for the neovascularization of tissue-engineered bladder. Adipose stromal vascular fraction (SVF) was isolated and used for the culture of ADEPCs and adipose derived stem cells (ADSCs). After SVF was cultured for one week, ADEPCs with typical cobblestone morphology emerged and could be isolated from ADSCs according to their different responses to trypsinization. Rat bladder smooth muscle cells (RBSMCs) were isolated and cultured from rat bladder. RBSMCs exhibited typical spindle-shaped morphology. ADEPCs had higher proliferative potential than ADSCs and RBSMCs. ADEPCs stained positive for CD34, Stro-1, VEGFR-2, eNOS and CD31 but negative for α-SMA, CD14 and CD45. ADSCs stained positive for CD34, Stro-1 and α-SMA but negative for VEGFR-2, eNOS, CD31, CD14 and CD45. RBSMCs stained only positive for α-SMA. ADEPCs could be expanded from a single cell at an early passage to a cell cluster containing more than 10,000 cells. ADEPCs were able to uptake DiI-Ac-LDL, bind UEA-1 and form capillary-like structures in three-dimensional scaffolds (Matrigel and bladder acellular matrix). ADEPCs were also able to enhance the human umbilical vein endothelial cells’ capability of capillary-like tube formation on Matrigel. Additionally, significantly higher levels of mRNA and protein of vascular endothelial growth factor were found in ADEPCs than in RBSMCs. These results suggest the potential use of ADEPCs as angiogenic cell sources for engineering bladder tissue.

The purpose of the present meta-analysis was to evaluate the efficacy and safety of testosterone replacement therapy in men with hypogonadism. A search was conducted for appropriate randomized controlled trials and the data from 16 trials were pooled. The intended primary outcome of the present study was to determine the efficacy and safety of testosterone replacement therapy. The current data demonstrated that scores for Aging Male Symptoms (AMS) were significantly reduced following testosterone replacement therapy, with a mean decrease in AMS score of 1.52 [95% confidence interval (CI), 0.72 to 2.32; P=0.0002]. Testosterone replacement therapy increased lean body mass [mean difference (MD), 1.22; 95% CI, 0.33 to 2.11; P=0.007], reduced fat mass in a non‑significantly manner (MD, ‑0.85; 95% CI, ‑1.74 to 0.04; P=0.06) and significantly reduced total cholesterol (MD, ‑0.16; 95% CI, ‑0.29 to ‑0.03; P=0.01). No significant differences were identified in body weight (MD, 0.09; 95% CI, ‑1.13 to 1.31; P=0.89), body mass index (MD, 0.10; 95% CI, ‑0.62 to 0.82; P=0.78) or bone mineral density (MD, ‑0.01; 95% CI, ‑0.03 to 0.02; P=0.60). Average prostate volume increased (MD, 1.58; 95% CI, 0.6 to 2.56; P=0.002) following testosterone replacement therapy, but the levels of prostate‑specific antigen (PSA) (MD, 0.10; 95% CI, ‑0.03 to 0.22; P=0.14) and the International Prostate Symptom Scores (MD, 0.01; 95% CI, ‑0.37 to 0.39; P=0.96) did not change. In conclusion, testosterone replacement therapy improves quality of life, increases lean body mass, significantly decreases total cholesterol, and is well‑tolerated and safe for men with hypogonadism who are exhibiting PSA levels of <4 ng/ml.

Background: Non-muscle invasive bladder cancer (NMIBC) represents the majority of bladder neoplasms. It is unusual for NMIBC metastasizing distantly without regional progression, namely metastatic NMIBC (mNMIBC), which is still poorly understood and easily omitted based on current management policies. So far, description of mNMIBC is limited to a few case reports. Methods: We reported a 70-year-old man with NMIBC who suffered from cervical metastasis without pelvic recurrence at 41 months after initial diagnosis. Then we performed a collective analysis of this case together with published mNMIBC cases searched from PubMed, Embase, and Web of Science, aiming to illustrate baseline clinicopathologic parameters, metastatic patterns, and treatment outcomes of these patients and analyze associated influencing factors. Results: After scrupulous review, 45 cases previous reported and the one from our center were incorporated into the aggregated cohort of mNMIBC, including 34 males and 12 females. Primary tumors from 46.7% of patients were high-grade (HG) or grade 3 (G3) and 65.1% had T1 lesions. Aberrant biomarker expression was found in tumors of some cases. Most (40/46) metastases of mNMIBC occurred at a single site, mainly in lung, bone and lymph nodes. Apart from three cases of de novo mNMIBC, the mean metastasis-free survival (MFS) interval of metachronous mNMIBC was 42.5 months, which was obviously longer than conventional metastatic bladder cancer. Shortened MFS interval was associated with old age, T1 or HG/G3 primary tumors, and non-lung metastases. Systemic chemotherapy and metastasectomy or radiotherapy for oligometastatic lesion were main therapeutic approaches of mNMIBC, and immunotherapy was adopted for the case from our center. Lung and bone metastases correlated with relatively favorable and unfavorable survival outcomes, respectively. Compared with monotherapy, chemotherapy, or immunotherapy combined with local cytoreduction got more favorable outcomes. Conclusion: Although rare, mNMIBC occurs more in tumors with high-risk features. Usually, mNMIBC metastasizes later than conventional metastatic bladder cancer and manifests as solitary lesion. Outcomes of mNMIBC would be influenced by metastatic site and post-metastatic treatment. Systemic treatment combined with local cytoreduction may render survival benefit in selected patients.

Prostate cancer (PCa) metastasis has emerged as a leading cause of mortality globally. Owing to the distinctive looping structure, circular RNA has become an ideal biological tumor marker. Here we investigate the mechanism and function of circular RNA, specifically circCNOT6L, on PCa metastasis. A loss-of-function assay was conducted in vitro to assess the impact of circCNOT6L on cancer cell proliferation, migration, invasion and ferroptosis. In addition, a xenograft mouse model was used to elucidate the influence of circCNOT6L on subcutaneous tumor xenograft and lung metastasis. Biochemical experiments elucidated the molecular mechanism by which circCNOT6L promotes malignant progression in PCa cells by modulating ferroptosis. Moreover, the combination of circCNOT6L-si and a ferroptosis activator was tested in organoids to evaluate their potential as suppressors of tumorigenesis. The novel circular RNA, circCNOT6L, was highly expressed in both PCa metastatic tissues and cells. circCNOT6L suppression resulted in a notable inhibition in PCa cell migration, invasion and ferroptosis in vitro. Furthermore, circCNOT6L inhibition hindered the growth and metastasis of mouse xenografts. Mechanistically, circCNOT6L, generated by the RNA-binding protein EIF4A3, competes with miR-143-5p for binding, thereby facilitating SRSF2-dependent splicing of SLC7A11 precursor RNA. This process inhibited ferroptosis in PCa cells and promoted PCa progression. Finally, inhibiting circCNOT6L overexpression in combination with the ferroptosis activator (erastin) significantly suppressed the viability of PCa-derived organoids. In conclusion, in the present study, we found that circCNOT6L induced by EIF4A3 through the SRSF2–SLC7A11 axis effectively inhibits ferroptosis, which in turn promotes malignant progression of PCa.