NEAT1 promotes the progression of prostate cancer by targeting the miR-582-5p/EZH2 regulatory axis.

In several forms of malignant tumors, nuclear enriched abundant transcript 1 (NEAT1), a lncRNA, has been identified to play an important role. NEAT1's regulation patterns in prostate cancer (PCa) are, however, mainly unknown. This study was aimed to evaluate and study the roles and regulatory mechanisms of NEAT1 in PCa. NEAT1, miR-582-5p, and enhancer of zeste homolog 2 (EZH2) expression were detected by qRT-PCR. The PCa cells' invasive, migrative, and proliferative activities in vitro were assessed using transwell migration and invasion, wound-healing, cloning creation, and CCK-8 assays. In the present study, impaired proliferative, migrative, and invasive capacities were observed in the NEAT1-deficient PCa (PC3 and LNCaP) cells. Further mechanistic studies found that NEAT1 performs its function through sponging miR-582-5p. Furthermore, EZH2 was confirmed to be the downstream target gene of miRNA-582-5p. The impaired progression caused by NEAT1 deficiency in PCa cells was significantly restored by the inhibition of miR-582-5p, while these effects were largely abolished by the deletion of EZH2. Finally, the xenograft nude mouse model showed that knocking down the expression of NEAT1 suppressed the growth of PCa. In conclusion, NEAT1 promotes the progression of PCa by controlling the miR-582-5p and miR-582-5p-mediated EZH2. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-023-00612-z.

The efficacy and safety of Hyperthermia intravesical chemotherapy in the treatment non-muscle invasive bladder cancer:A meta analysis.

Background：The current treatment of non-muscle-invasive bladder cancer is suboptimal. However, in recent years, hyperthermia intravesical chemotherapy has emerged as a more effective alternative to conventional bladder perfusion. This novel treatment approach appears to have a similar therapeutic effect as BCG perfusion. Objective: This study aims to evaluate the safety and effectiveness of hyperthermia intravesical chemotherapy compared to conventional bladder perfusion chemotherapy for non-muscle-invasive bladder cancer. Additionally, it aims to evaluate the safety and effectiveness of hyperthermia intravesical chemotherapy in comparison to BCG perfusion therapy for non-muscle-invasive bladder cancer. Methods：We conducted a comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science databases to gather relevant studies on hyperthermia intravesical chemotherapy for non-muscle-invasive bladder cancer. The analysis of the collected data was carried out using RevMan 5.3 software. Results：A total of 8 randomized controlled trials (RCTs) were included in this meta-analysis, involving 1203 patients. Among them, 629 cases received hyperthermia intravesical chemotherapy (HIVEC), 419 cases received conventional bladder perfusion chemotherapy with mitomycin C (MMC), and 155 cases received Bacillus Calmette-Guérin (BCG). The combined analysis revealed that the recurrence rate of bladder hyperthermic perfusion was significantly lower than that of conventional perfusion chemotherapy (RR=0.65, 95%CI 0.52-0.82, P=0.0003). However, there was no significant difference in recurrence rate between hyperthermia intravesical chemotherapy and BCG perfusion (RR=0.78, 95%CI 0.56-1.09, P=0.14). Furthermore, no significant difference was found in the progression rate between the hyperthermia intravesical chemotherapy group and either the conventional bladder chemotherapy group (RR=1.08, 95%CI 0.52-2.26, P=0.83) and the BCG perfusion group (RR=0.48, 95%CI 0.19-1.25, P=0.13). However, Compared with the conventional bladder perfusion chemotherapy group, there was no significant statistical difference in adverse events between the bladder hyperthermia chemotherapy group and the conventional bladder perfusion chemotherapy group (RR1.08, 95% CI 0.80,1.45, p=0.63). No significant difference in the incidence of adverse events was observed between hyperthermia intravesical chemotherapy and BCG perfusion (RR1.03, 95% CI 0.83,1.29, p=0.79).

ZNF692 promotes cell proliferation, invasion and migration of human prostate cancer cells by targeting the EMT signaling pathway.

BACKGROUND: Prostate cancer poses a considerable threat to human health. At present, the mechanism of tumor progression remains unclear. ZNF692 is overexpressed in many tumors, and the high expression of ZNF692 is correlated with tumor aggressiveness and tumor phenotype of prostate cancer, suggesting that ZNF692 may play an important role in tumor biology of prostate cancer. This paper aims to elucidate the relationship between them. METHODS: The expression level of ZNF692 was verified in normal prostate cells (RWPE-1) and prostate cancer cells (LNCaP, PC3, DU145). PC3 cells were selected to construct the ZNF692 knockout prostate cancer cell line. The changes of cell proliferation, apoptosis, invasion and metastasis were detected by CCK8, Edu staining, Transwell assay and scratch assay. The expression levels of related proteins were detected by Western blot. RESULTS: At the cellular level, ZNF692 was overexpressed to varying degrees in prostate cancer cell lines, with the highest expression in PC3 cell lines. CCK8 and Edu results showed that the proliferation of prostate cancer PC3 cells that knocked down ZNF692 was slowed. Transwell assay and scratch assay showed reduced invasion and migration of prostate cancer PC3 cells that knocked out ZNF692. Flow cytometry showed that the apoptosis rate of prostate cancer PC3 cells after ZNF692 knockout was increased. In addition, after ZNF692 silencing, the expression level of epithelial phenotype E-cadherin increased in PC3 cells, while the expression level of interstitial phenotype N-cadherin, Vimentin, c-Myc, and CyclinA1 decreased. The state of prostate cancer PC3 cells that overexpressed ZNF692 was reversed from the state after ZNF692 was knocked down. CONCLUSION: ZNF692 can be used as a new prognostic marker and a potential biologic therapeutic target for PCa. By inhibiting the expression of c-myc and cyclinA1, the EMT signaling pathway is regulated to provide evidence for its potential molecular mechanism.

Laparoscopic ureteroneocystostomy with bladder flap for benign ureteral stenosis: our initial experience.

To present our experience with laparoscopic ureteroneocystostomy with bladder flap (LUCBF) for treating benign ureteral stenosis and evaluate its feasibility and efficacy. The clinical data of 27 patients with benign ureteral stenosis who underwent LUCBF were retrospectively analyzed. After identification and excision of the ureteral stenosis segment, the healthy ureteral stump was dissected and incised longitudinally. A U-shaped or spiral bladder flap was harvested from the anterolateral bladder wall for ureteroplasty. All patients underwent LUCBF successfully, including 14 patients were combined with psoas hitch technique, between 90 and 220 min (median, 155 min). The median length of ureteral defect was 6 cm (range, 5-17 cm). The median blood loss was 40 ml (20-150 ml). The median indwelling time of double-J stent was 8 weeks (range, 4-8 weeks). Five patients (10.6%) suffered postoperative complications during the follow-up period (range, 12-48 months), including fever, hematuria, urinary tract infection and recurrent stenosis. The success rate was 96.3% (26/27). Patients with long ureter defects had longer operative time and more blood loss than short ureter defects. LUCBF was a safe and feasible technique for benign ureteral stenosis. Long ureter defect was related to longer operative time and more blood loss.

The role of the methyltransferase METTL3 in prostate cancer: a potential therapeutic target.

The incidence of prostate cancer (PCa), the most prevalent malignancy, is currently at the forefront. RNA modification is a subfield of the booming field of epigenetics. To date, more than 170 types of RNA modifications have been described, and N6-methyladenosine (m6A) is the most abundant and well-characterized internal modification of mRNAs involved in various aspects of cancer progression. METTL3, the first identified key methyltransferase, regulates human mRNA and non-coding RNA expression in an m6A-dependent manner. This review elucidates the biological function and role of METTL3 in PCa and discusses the implications of METTL3 as a potential therapeutic target for future research directions and clinical applications.

The role of RNA modification in urological cancers: mechanisms and clinical potential.

RNA modification is a post-transcriptional level of regulation that is widely distributed in all types of RNAs, including mRNA, tRNA, rRNA, miRNA, and lncRNA, where N6-methyladenine (m6A) is the most abundant mRNA methylation modification. Significant evidence has depicted that m6A modifications are closely related to human diseases, especially cancer, and play pivotal roles in RNA transcription, splicing, stabilization, and translation processes. The most common urological cancers include prostate, bladder, kidney, and testicular cancers, accounting for a certain proportion of human cancers, with an ever-increasing incidence and mortality. The recurrence, systemic metastasis, poor prognosis, and drug resistance of urologic tumors have prompted the identification of new therapeutic targets and mechanisms. Research on m6A modifications may provide new solutions to the current puzzles. In this review, we provide a comprehensive overview of the key roles played by RNA modifications, especially m6A modifications, in urologic cancers, as well as recent research advances in diagnostics and molecularly targeted therapies.

Comparison of traditional and novel tip-flexible suctioning ureteral access sheath combined with flexible ureteroscope to treat unilateral renal calculi.

OBJECTIVES: To compare the safety and efficacy of novel tip-flexible suctioning ureteral access sheath (NTFS-UAS) and traditional ureteral access sheath (T-UAS) combined with flexible ureteroscope for treating unilateral renal calculi. MATERIALS AND METHODS: The clinical data of 214 patients with unilateral renal calculi treated by NTFS-UAS (n = 102) and T-UAS (n = 112) combined with flexible ureteroscope from August 2021 to April 2022 were analyzed retrospectively. Demographic characteristics, stone-related parameters, operative time, stone-free rates (SFR), hospitalization time and complication rate (CR) were analyzed. RESULT: No significant difference was observed between the two groups in terms of demographic characteristics, stone-related parameters, intraoperative CR, and hospitalization time. The operative time of NTFS-UAS group was significantly shorter than T-UAS group (55.25 ± 11.42 min vs. 59.36 ± 15.59 min; P = 0.028). The NTFS-UAS group obtained significantly higher SFR on 1 day postoperatively (86.3% vs. 75.0%; P = 0.038), and higher SFR on 30 days postoperatively than T-UAS group (91.2% vs. 81.3%; P = 0.037). The hemoglobin loss of NTFS-UAS group (- 0.54 ± 0.69 g/dl) was significantly lower than T-UAS group (- 0.83 ± 0.66 g/dl; P = 0.002). There was a significantly lower incidence of overall CR (11.8% vs. 22.3%; P = 0.041), and infectious CR (8.8% vs. 18.8%; P = 0.037) in the NTFS-UAS group. CONCLUSION: Compared to T-UAS combined with flexible ureteroscope for treating unilateral renal calculi, NTFS-UAS had superiority in higher SFR on 1 day and 30 days postoperatively. Shorter operation time, lower hemoglobin loss, lower incidences of overall and infectious CR were observed in NTFS-UAS group. REGISTRATION NUMBER AND DATE: ChiCTR2300070210; April 5, 2023.

Therapeutic potential of vasculogenic mimicry in urological tumors.

Angiogenesis is an essential process in the growth and metastasis of cancer cells, which can be hampered by an anti-angiogenesis mechanism, thereby delaying the progression of tumors. However, the benefit of this treatment modality could be restricted, as most patients tend to develop acquired resistance during treatment. Vasculogenic mimicry (VM) is regarded as a critical alternative mechanism of tumor angiogenesis, where studies have demonstrated that patients with tumors supplemented with VM generally have a shorter survival period and a poorer prognosis. Inhibiting VM may be an effective therapeutic strategy to prevent cancer progression, which could prove helpful in impeding the limitations of lone use of anti-angiogenic therapy when performed concurrently with other anti-tumor therapies. This review summarizes the mechanism of VM signaling pathways in urological tumors, i.e., prostate cancer, clear cell renal cell carcinoma, and bladder cancer. Furthermore, it also summarizes the potential of VM as a therapeutic strategy for urological tumors.

Targeting integrin α5ß1 in urological tumors: opportunities and challenges.

Urological tumors, such as prostate cancer, renal cell carcinoma, and bladder cancer, have shown a significant rise in prevalence in recent years and account for a significant proportion of malignant tumors. It has been established that metastasis to distant organs caused by urological tumors is the main cause of death, although the mechanisms underlying metastasis have not been fully elucidated. The fibronectin receptor integrin α5ß1 reportedly plays an important role in distant metastasis and is closely related to tumor development. It is widely thought to be an important cancer mediator by interacting with different ligands, mediating tumor adhesion, invasion, and migration, and leading to immune escape. In this paper, we expound on the relationship and regulatory mechanisms of integrin α5ß1 in these three cancers. In addition, the clinical applications of integrin α5ß1 in these cancers, especially against treatment resistance, are discussed. Last but not least, the possibility of integrin α5ß1 as a potential target for treatment is examined, with new ideas for future research being proposed.

Preclinical models and evaluation criteria of prostatitis.

Prostatitis is a common urological condition that affects almost half of all men at some point in their life. The prostate gland has a dense nerve supply that contributes to the production of fluid to nourish sperm and the mechanism to switch between urination and ejaculation. Prostatitis can cause frequent urination, pelvic pain, and even infertility. Long-term prostatitis increases the risk of prostate cancer and benign prostate hyperplasia. Chronic non-bacterial prostatitis presents a complex pathogenesis, which has challenged medical research. Experimental studies of prostatitis require appropriate preclinical models. This review aimed to summarize and compare preclinical models of prostatitis based on their methods, success rate, evaluation, and range of application. The objective of this study is to provide a comprehensive understanding of prostatitis and advance basic research.

Impact of SOX2 function and regulation on therapy resistance in bladder cancer.

Bladder cancer (BC) is a malignant disease with high rates of recurrence and mortality. It is mainly classified as non-muscle-invasive BC and muscle-invasive BC (MIBC). Often, MIBC is chemoresistant, which, according to cancer stem cells (CSCs) theory, is linked to the presence of bladder cancer stem cells (BCSCs). Sex-determining region Y- (SRY) Box transcription factor 2 (SOX2), which is a molecular marker of BCSCs, is aberrantly over-expressed in chemoresistant BC cell lines. It is one of the standalone prognostic factors for BC, and it has an inherently significant function in the emergence and progression of the disease. This review first summarizes the role of SRY-related high-mobility group protein Box (SOX) family genes in BC, focusing on the SOX2 and its significance in BC. Second, it discusses the mechanisms relevant to the regulation of SOX2. Finally, it summarizes the signaling pathways related to SOX2 in BC, suggests current issues to be addressed, and proposes potential directions for future research to provide new insights for the treatment of BC.

CD36 and Its Role in Regulating the Tumor Microenvironment.

CD36 is a transmembrane glycoprotein that binds to a wide range of ligands, including fatty acids (FAs), cholesterol, thrombospondin-1 (TSP-1) and thrombospondin-2 (TSP-2), and plays an important role in lipid metabolism, immune response, and angiogenesis. Recent studies have highlighted the role of CD36 in mediating lipid uptake by tumor-associated immune cells and in promoting tumor cell progression. In cancer-associated fibroblasts (CAFs), CD36 regulates lipid uptake and matrix protein production to promote tumor proliferation. In addition, CD36 can promote tumor cell adhesion to the extracellular matrix (ECM) and induce epithelial mesenchymal transition (EMT). In terms of tumor angiogenesis, CD36 binding to TSP-1 and TSP-2 can both inhibit tumor angiogenesis and promote tumor migration and invasion. CD36 can promote tumor angiogenesis through vascular mimicry (VM). Overall, we found that CD36 exhibits diverse functions in tumors. Here, we summarize the recent research findings highlighting the novel roles of CD36 in the context of tumors.

Obesity-Related Cross-Talk between Prostate Cancer and Peripheral Fat: Potential Role of Exosomes.

The molecular mechanisms of obesity-induced cancer progression have been extensively explored because of the significant increase in obesity and obesity-related diseases worldwide. Studies have shown that obesity is associated with certain features of prostate cancer. In particular, bioactive factors released from periprostatic adipose tissues mediate the bidirectional communication between periprostatic adipose tissue and prostate cancer. Moreover, recent studies have shown that extracellular vesicles have a role in the relationship between tumor peripheral adipose tissue and cancer progression. Therefore, it is necessary to investigate the feedback mechanisms between prostate cancer and periglandular adipose and the role of exosomes as mediators of signal exchange to understand obesity as a risk factor for prostate cancer. This review summarizes the two-way communication between prostate cancer and periglandular adipose and discusses the potential role of exosomes as a cross-talk and the prospect of using adipose tissue as a means to obtain exosomes in vitro. Therefore, this review may provide new directions for the treatment of obesity to suppress prostate cancer.

Clinical potential of the Hippo-YAP pathway in bladder cancer.

Bladder cancer (BC) is one of the world's most frequent cancers. Surgery coupled with adjuvant platinum-based chemotherapy is the current standard of therapy for BC. However, a high proportion of patients progressed to chemotherapy-resistant or even neoplasm recurrence. Hence, identifying novel treatment targets is critical for clinical treatment. Current studies indicated that the Hippo-YAP pathway plays a crucial in regulating the survival of cancer stem cells (CSCs), which is related to the progression and reoccurrence of a variety of cancers. In this review, we summarize the evidence that Hippo-YAP mediates the occurrence, progression and chemotherapy resistance in BC, as well as the role of the Hippo-YAP pathway in regulating bladder cancer stem-like cells (BCSCs). Finally, the clinical potential of Hippo-YAP in the treatment of BC was prospected.

Tumor-Promoting ATAD2 and Its Preclinical Challenges.

ATAD2 has received extensive attention in recent years as one prospective oncogene with tumor-promoting features in many malignancies. ATAD2 is a highly conserved bromodomain family protein that exerts its biological functions by mainly AAA ATPase and bromodomain. ATAD2 acts as an epigenetic decoder and transcription factor or co-activator, which is engaged in cellular activities, such as transcriptional regulation, DNA replication, and protein modification. ATAD2 has been reported to be highly expressed in a variety of human malignancies, including gastrointestinal malignancies, reproductive malignancies, urological malignancies, lung cancer, and other types of malignancies. ATAD2 is involved in the activation of multiple oncogenic signaling pathways and is closely associated with tumorigenesis, progression, chemoresistance, and poor prognosis, but the oncogenic mechanisms vary in different cancer types. Moreover, the direct targeting of ATAD2's bromodomain may be a very challenging task. In this review, we summarized the role of ATAD2 in various types of malignancies and pointed out the pharmacological direction.