Background: Prostate cancer (PCa) is one of the leading causes of male morbidity and mortality due to malignant disease?throughout the world. Recently, circRNAs have been considered as important regulators?in tumorigenesis related networks. Nevertheless, the?biological role and expression pattern of circRNA-ITCH (circ-ITCH) in prostate cancer are still not fully understood. Objectives: The purpose of the present study was to determine circ-ITCH expression?in prostate cancer tissues and cell lines and analyze its potential regulatory effects on the proliferation, apoptosis, migration and invasion of prostate cells in-vitro. Methods: The expression of circ-ITCH was detected in 6 pairs of PC tissues and adjacent?normal tissues (n = 6) as well as PC cell lines by quantitative real-time PCR. The function of circ-ITCH was assessed by?gain-of-function experiments. Cell proliferation and colony-forming efficiency were assessed using Cell Counting Kit-8 and plate cloning?assays, respectively. The migratory and invasive abilities were?examined via Wound Healing and Transwell assay and Annexin V-FITC/propidium iodide (PI) staining was used to assess apoptosis. Bioinformatic analysis in combination with dual-luciferase reporter analysis was performed to validate the regulatory?relationships between circ-ITCH, miR-106b-5p and SETD2. Results: Relative to the corresponding control group, circ-ITCH expression?was markedly decreased in prostate cancer tissues and cell lines. In-vitro, circ-ITCH overexpression inhibited cell?proliferation and clonogenicity and increased the number of apoptotic cells in prostate cancer. Moreover, circ-ITCH overexpression reduced cell migration and invasion abilities. The luciferase reporter assays confirmed that circ-ITCH was?the target of miR-106b-5p and miR-106b-5p targeted SETD2. circ-ITCH upregulation was?correlated with elevated SETD2 expression, which is in line with a miR-106b-5p–dependent pattern of regulation. Conclusion: These findings suggest that circ-ITCH can modulate malignant cell phenotypes (proliferation, apoptosis, migration and invasion) in PCa cells in-vitro through the?miR-106b-5p/SETD2 axis. There are only a limited number of tissue samples and?in-vitro experimental designs in our study and more experiments will be needed to further confirm these findings and reveal the biological significance.

Objective: To evaluate the clinical efficacy of combined cystoscopy and laparoscopy for vesicovaginal fistula repair in a single position. Methods: A retrospective analysis was conducted on the clinical data of 6 patients with vesicovaginal fistula treated in the Department of Urology, The First Affiliated Hospital of Jinan University from August 2017 to November 2023. All patients underwent a single-position cystoscopy combined with laparoscopic vesicovaginal fistula repair. Intraoperatively, the fistula was localized transurethrally via cystoscopy, and place ureteral stents. Simultaneously, laparoscopic repair of the fistula was performed via abdominal approach. Recording Surgical duration, intraoperative blood loss, length of hospital stay, intraoperative complications and postoperative complications. Results: All 6 patients underwent successful repair without conversion to open surgery. Operative time was 263.5±49.6 min, intraoperative blood loss was 35.0±20.7 ml, hospital stay was 15.5±5.4 days. At follow-up ranging from 3 to 12 months, no patients developed complications such as urinary leakage, and postoperative quality of life showed significant improvement. Conclusion: Combined cystoscopy and laparoscopy for vesicovaginal fistula repair in a single position avoids multiple repositioning, offering advantages such as simplified technique, short operative time, minimal trauma, and reducedloss blood. This approach represents a safe and effective therapeutic modality.

Background:Postoperative cognitive dysfunction (POCD) is driven in part by microglial activation and the resulting neuroinflammatory response. Emerging evidence suggests that microRNAs regulate key inflammatory pathways in the central nervous system. In this study, we examined the role of the mmu‑miR‑125a/TRAF6 signaling axis in microglial activation under inflammatory conditions induced by lipopolysaccharide (LPS) and surgical trauma and evaluated whether dexmedetomidine (DEX) modulates this pathway to alleviate POCD. Methods:Murine microglial cells were treated with LPS to induce activation. Expression levels of mmu‑miR‑125a and TRAF6 were quantified by qRT‑PCR and Western blotting. Bioinformatic prediction of miRNA binding sites was performed, and a luciferase reporter assay was used to confirm direct targeting of TRAF6 by mmu‑miR‑125a. Adult mice underwent standardized surgical trauma to induce POCD. Brain tissues were analyzed for microglial activation markers, cytokine levels, and expression of mmu‑miR‑125a and TRAF6. DEX was administered in both in vitro and in vivo models. The effects on cytokine release, microglial activation, and the mmu‑miR‑125a/TRAF6 axis were assessed. Results:Our findings revealed significant alterations in the expression levels of TRAF6 and mmu-miR-125a during LPS-induced microglial activation. Through bioinformatics analysis and experimental validation, we identified TRAF6 as a direct target of mmu-miR-125a. The mmu-miR-125a/TRAF6 axis was found to be crucial for regulating microglial activation both in vitro, using an LPS-induced model, and in vivo, using a surgical trauma-induced POCD model. Moreover, we demonstrated that DEX, an alpha-2 adrenergic receptor agonist, effectively modulated the inflammatory cytokine release by targeting the mmu-miR-125a/TRAF6 axis in both models. The administration of DEX significantly suppressed microglial activation and TRAF6 expression, effects that were reversed by the inhibition of mmu-miR-125a. Conclusion:Our study provides new insights into the molecular mechanisms underlying microglial activation and highlights the therapeutic potential of targeting the mmu-miR-125a/TRAF6 axis to alleviate neuroinflammation by the administration of DEX in POCD.

Background:Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignant tumor. Currently, there is a lack of reliable prognostic markers in clinical practice. Extensive research has shown that long non-coding RNA (lncRNA) are critical factors in the initiation and progression of cancer, closely associated with early diagnosis and prognosis. Previous studies have identified that ZFHX4 antisense RNA 1 (ZFHX4-AS1) is aberrantly expressed in various cancers and is associated with poor outcomes. This study investigates whether ZFHX4-AS1 affects the prognosis of ACC patients and, if so, the potential mechanisms involved. Methods:In this study, utilizing four multi-center cohorts from The Cancer Genome Atlas (TCGA) program and Gene Expression Omnibus (GEO), we validated the prognostic capability of ZFHX4-AS1 in ACC patients through Kaplan-Meier survival analysis, cox regression models, and nomograms. Then, we explored the biological functions of ZFHX4-AS1 using gene set enrichment analysis (GSEA), competing endogenous RNA (ceRNA) networks, and analyses of somatic mutations and copy number variation (CNV). Finally, in vitro experiments were conducted to further validate the impact of ZFHX4-AS1 on proliferation and migration capabilities of ACC cell lines. Results:Survival analysis indicated that patients in the high ZFHX4-AS1 expression group of ACC had worse prognosis. Cox regression analyses suggested that ZFHX4-AS1 levels were independent risk factors for prognosis. Subsequently, we constructed nomograms based on clinical features and ZFHX4-AS1 levels, demonstrating good predictive performance under the time-dependent receiver operating characteristic (ROC) curve. Analysis based on somatic mutations and CNV revealed that CTNNB1 and 9p21.3-Del drove the expression of ZFHX4-AS1. Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays confirmed that knockdown of ZFHX4-AS1 inhibited proliferation and migration of ACC cells. Conclusions:This study demonstrates that ZFHX4-AS1 has a reliable predictive value for the prognosis of ACC patients and is a promising biomarker.

Prostate cancer (PCa) is a prevalent malignancy among men worldwide, and biochemical recurrence (BCR) after radical prostatectomy (RP) is a critical turning point commonly used to guide the development of treatment strategies for primary PCa. However, the clinical parameters currently in use are inadequate for precise risk stratification and informing treatment choice. To address this issue, we conducted a study that collected transcriptomic data and clinical information from 1662 primary PCa patients across 12 multicenter cohorts globally. We leveraged 101 algorithm combinations that consisted of 10 machine learning methods to develop and validate a 9-gene signature, named BCR SCR, for predicting the risk of BCR after RP. Our results demonstrated that BCR SCR generally outperformed 102 published prognostic signatures. We further established the clinical significance of these nine genes in PCa progression at the protein level through immunohistochemistry on Tissue Microarray (TMA). Moreover, our data showed that patients with higher BCR SCR tended to have higher rates of BCR and distant metastasis after radical radiotherapy. Through drug target prediction analysis, we identified nine potential therapeutic agents for patients with high BCR SCR. In conclusion, the newly developed BCR SCR has significant translational potential in accurately stratifying the risk of patients who undergo RP, monitoring treatment courses, and developing new therapies for the disease.

Abstract Bacnkground Approximately 15% of patients with prostate cancer (PCa) are diagnosed with high-risk disease and will face sequelae of diagnosis and treatment. Recently, aberrant expression of circular RNA-ITCH (circ-ITCH) may be associated with the risk of lymph node metastasis and poorer prognosis in tumor patients. The mechanism underlying the role of circ-ITCH in the progression and development of PCa is still under investigation.Objective To elucidate the functional role of the circ-ITCH gene in PCa, assess its possible predictive/prognostic molecular biomarkers of PCa, and possible molecular mechanisms of action.Methods In this study, we collected six sets of paired PCa and normal tissue specimens to explore the relationship between circ-ITCH expression and PCa development; Cell growth was assessed by the Cell Counting Kit-8 assay and cell clone formation assay; Transwell assays were performed to evaluate cell migration and invasion; Apoptotic cells were detected by Annexin-V-isothiocyanate fluorescein and propidium iodide staining; Target gene prediction and screening, luciferase reporter gene assays were utilized to confirm the relationship between circ-ITCH and microRNA.Results In the present study, we found that circ-ITCH, is down-regulated in PCa tissues and cell lines. Moreover, enforced-expression of circ-ITCH inhibited cell proliferation, migration, invasion and metastasis in vitro . Mechanistically, we demonstrate that circ-ITCH upregulates the expression of the target gene SETD2 by 'sponging' miR-106b-5p, which suppressed the aggressive biological behaviors of PCa.Conclusions Circ-ITCH inhibits PCa cell proliferation and metastasis by negatively regulating the miR-106b-5p/SETD2 axis.

Objective:To investigate the clinical efficacy of early electrophysiological technology intervention in restoring urine control function after laparoscopic radical resection of prostate cancer.Methods:Five patients aged (63.20±6.14) years with prostate cancer enrolled in the Department of Urology of The First Affiliated Hospital of Jinan University from July to December 2021 received electrophysiological intervention on the third day after laparoscopic radical resection of prostate cancer. The laparoscopic radical resection of prostate cancer was performed between pelvic fascia and prostatic fascia. Tension-free anastomosis was made between the bladder and proximal urethra, and then the anterior wall of the bladder neck and the pubic prostate ligament were stitched up. On the third day, a medical infrared thermal imaging instrument (PRISM 640A/PRISM 384A) was used to visualize the electrophysiological diagnosis, the individual electrophysiological parameters were selected, and then the precise electrophysiological treatment was conducted (low-frequency neuromuscular therapy instrument model: BioStim pro and BioStim ble Foshan Shanshan Datang Medical Technology Co., LTD.). Electrophysiological treatment parameters and electrode tablet adhesive locations: BB8: 10 Hz/300 μs for arterial circulation, BB16: 2 Hz/280 μs for venous circulation, BB27: 48 Hz/180 μs for arterial circulation, BB30: 10 Hz/480 μs for lymphatic circulation; EE21: 36 Hz/300 μs for vascular smooth muscle; electrode tablets were affixed at "curved bone, triple Yin" acupoints. DD1: 8 Hz/500 μs, 20 Hz/350 μs for classⅠ skeletal muscle, DD211: 25 Hz/500 μs for classⅠ skeletal muscle, DD297: 36 Hz/350 μs for class Ⅱ skeletal muscle, DD211 and DD297 alternatively; electrode tablets were attached to the pelvic floor muscles. CC16: 25 Hz/300 μs for pudendal nerves, CC39: 96 Hz/150 μs for sympathetic nerves, electrode tablets were affixed to the "curved bone, sacral eight points" acupoints, consecutive treatment for 5-9 times. After treatment, International Incontinence Advisory Committee Incontinence Questionnaire (ICI-Q-SF) score, Quality of Incontinence Questionnaire (I-QOL) score, and 24 h urinary pad usage in the five patients were recorded.Results:All the patients completed the operation successfully, with the operation time of (5.92±1.35) h, the bleeding volume of (42.00±10.95) ml, and the pelvic drainage tube duration of (4.20±1.10) d. One patient had fever and was cured according to the symptoms. Two weeks later, all the 5 patients had a little urine leakage when coughing vigorously after urinary catheters were removed. Only one patient applied 1 urinary pad on the very day of the extraction of urine tube, and the urinary pad utilized by the patient was less than or equal to 1 piece within 24 hours; another 4 patients did not use the urinary pad after extraction of urine tube, whom were evaluated as the postoperative early recovery of urine control function. The treatment cycle was (7.40±1.52) d, the ICI-Q-SF score was (2.80±1.64), and the I-QOL score was (94.00±3.08).Conclusion:The early electrophysiological technology intervention in restoring urine control function after laparoscopic radical resection of prostate cancer is safe and effective, and it might be expected to become a standard adjuvant therapy in the future.

LncRNAs involve in the autophagy to regulate prostate cancer (PCA) initiation and progression. Therefore, it urges to explore more significant AR-lncRNAs in PCa. mRNA data and clinical information of PCa were achieved from TCGA database, and ARGs were obtained from the HADb. AR-lncRNAs were identified by correlation analysis of DE ARGs and lncRNAs. Univariate Cox regression, LASSO regression, and multivariate Cox regression were used to identify the prognostic AR-lncRNA signature and constructed a risk model. GESA was used to biological function analysis between high- and low-risk score group. A nomogram was constructed and used to predicate the survival of PCa patients. A calibration curve was used to determine the accuracy of the predication model. AR-related ceRNA network was constructed by correlation analysis. Expression of six AR-related lncRNAs were detected by qRT-PCR. 222 ARGs and 385 AR-lncRNAs were screened from PCa and normal tissues, and 17 AR-lncRNAs were identified as prognostic signature for PCa. Based on the expression of prognostic signature, a risk score was calculated, and PCa samples were distributed into high- and low-risk score groups. The biological function and predicated value of the prognostic signature were also examined. Finally, based on the correlation between each ARG and its prognostic signature, three modules of AR-lncRNA-miRNA-mRNA regulatory networks were constructed based on 6 AR-lncRNAs, 17 miRNAs, and 12 ARGs. And we found that AC012085.2, UBXN10-AS1, LINC00261 downregulated, whereas AP004608.1, AC104667.2, AC008610.1 upregulated in PCa compared with BPH tissues. Our finding supplied the potential AR-lncRNAs prognostic signature for PCa.

目的:探索单酰甘油脂酶(MGLL)在前列腺癌(PCa)中的表达及其临床预后.方法:利用基因表达谱交互分析(GEPIA),Oncomine及人类蛋白质图谱(THPA)生物信息学工具,分析癌症公共数据库TCGA及GEO中PCa及对照样本中MGLL的mRNA及蛋白表达情况,基于TCGA数据库中的PCa病人样本信息进行生存分析,观察MGLL与成纤维细胞生长因子(FGF)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号通路中关键蛋白的共表达相关性.通过Western blot检测MGLL在PCa细胞系中的表达;通过Transwell检测过表达MGLL对PCa细胞系迁移和侵袭的作用.结果:Oncomine数据库中检索到6组PCa研究队列,GEPIA工具共有492例PCa样本及52例前列腺对照样本.发现在Oncomine的多个PCa队列研究中,与对照前列腺组织相比,MGLL mRNA在PCa组织中显著低表达(P＜0.021).GEPIA分析的TCGA队列显示,MGLL在PCa中的mRNA水平亦显著降低(P＜0.01).THPA在线工具表明,MGLL蛋白在正常前列腺组织中高表达,而在PCa组织中低表达.蛋白水平与mRNA水平趋势一致.GEPIA的生存分析表明,MGLL表达水平与PCa患者总生存期(OS)和无瘤生存期(DFS)密切相关,MGLL低表达患者的预后较差(P=0.018;P=0.034).蛋白共表达分析表明,PCa中MGLL与FGF受体FGFR1、PIK3CA、AKT2、GSK-3B及CRMP2均成正相关(R=0.6,P=0;R=0.36,P=0;R=0.22,P＜0.001;R=0.36,P=0;R=0.5,P=0).Western blot检测表明MGLL在多个PCa细胞系中低表达,且过表达MGLL会抑制PCa细胞的迁移和侵袭能力(P＜0.05).结论:MGLL在PCa组织及癌细胞系中低表达,且与癌患者预后相关,其机制可能与PI3K/AKT/GSK-3B信号通路相关.

Prostate cancer (PCa) is a serious disease that affects men’s health. To date, no effective and long-lasting treatment option for this condition is available in clinical practice. ANT2 is highly expressed in a variety of hormone-related cancers, but its relationship and regulatory mechanism with PCa are unclear. In this study, we found that ANT2 expression was significantly upregulated in PCa tissues relative to control samples. Genetic knockdown of ANT2 effectively inhibited, while overexpression promoted, proliferation, migration, and invasion of PCa cells. In addition, miR-137 expression was reduced in prostate cancer tissues relative to control tissues. We identified a regulatory site for miR-137 in the 3′-UTR of ANT2 mRNA; luciferase reporter assays indicated that ANT2 is a direct target gene for miR-137. Transfecting cells with miR-137 mimics and/or an ANT2-encoding plasmid revealed that ANT2 promotes proliferation, migration, and invasion of PCa, whereas co-expression of miR-137 mimics inhibited these behaviors. These observations suggest that miR-137 mimics inhibit development of PCa by antagonizing expression of ANT2. Furthermore, tumorigenic assays in nude mice showed that miR-137 inhibitors abolished the inhibitory effect of ANT2 knockdown on PCa tumor growth. Collectively, our findings suggest that ANT2, a target gene of miR-137, is intimately involved in development of PCa, providing new evidence for the mechanism underlying pathogenesis of PCa as well as new options for targeted therapy.

很多中老年人一天之中要频繁去厕所,不过,拼命使劲也无法顺畅排尿,好不容易把尿憋出来却是一滴一滴地滴沥出来,晚上时常折腾. 中老年男性的尿频、尿急、夜尿多等,很多时候就是前列腺增生的问题,不适症状是一个缓慢加重的过程,因此尽早根据病情轻重进行合理治疗非常重要.

Prostate cancer is the most common malignant tumor of the urinary system. The mechanisms of the initiation and progression of prostate cancer have not been fully elucidated. Increasing evidence suggests that circular RNAs (circRNAs) are involved in cancer pathogenesis. In this study, we aimed to identify differentially expressed circRNAs in prostate cancer tissues and explored the role of circRNAs in the pathogenesis of prostate cancer. By screening a circRNA microarray assay, we found that circ_0088233 was upregulated in prostate cancer tissues compared to adjacent normal tissues, and this upregulation can be verified in 46 pairs of prostate cancer and adjacent normal tissues examined using quantitative reverse transcription-PCR. The level of circ_0088233 correlated with the TNM stage. Knockdown of circ_0088233 reduced cell proliferation, migration, invasion, and induced G1 phase arrest and apoptosis. In addition, miR-185-3p was identified as the downstream target of circ_0088233 using luciferase reporter assays and a biotinylated circ_0088233 probe pull-down assay. The miR-185-3p level showed a negative correlation with the circ_0088233 level in prostate cancer tissues. Overexpression of circ_0088233 blocked the effects of miR-185-3p on cell proliferation, migration, invasion, cell cycle, and apoptosis. In conclusion, circ_0088233 may function as an oncogene and play an oncogenic role by sponging hsa-miR-185-3p. This study increases the understanding of circRNAs in the progression of prostate cancer. These results implicate circ_0088233 as a potential therapeutic target for prostate cancer.

OBJECTIVE To study the expression of BIRC6 in renal cancer tissues and investigate the effect of BIRC6 silencing on apoptosis and autophagy of 786-O cells. METHODS Twenty surgical specimens of renal cancer tissues and adjacent renal tissues were collected from Meizhou People's Hospital between February, 2016 and December, 2018 for detection of BIRC6 protein expression using immunohistochemistry. Renal cancer 786-O cells were transfected with a control small interfering RNA (siRNA) or BIRC6 siRNA via lipofectamine 2000, and the changes in cell proliferation and apoptosis following 5-FU treatment were assessed using CCK8 assay and flow cytometry; the expressions of autophagy-related proteins Beclin and LC3A/B were detected by Western blotting. RESULTS The expression of BIRC6 protein was significantly higher in renal cancer tissues than in the adjacent renal tissues. Western blotting showed that siRNA-mediated silencing of BIRC6 significantly lowered the expression of BIRC6 in 786-O cells. In the cells with BIRC6 silencing, treatment with 12.5, 25, 50, 100 and 200 μg/mL 5-FU resulted in significantly higher proliferation inhibition rates than in the cells transfected with the control siRNA (P < 0.01). BIRC6 silencing also significantly increased the apoptosis rate of 786-O cells following 5-FU treatment (P < 0.01). The results of Western blotting showed that BIRC6 silencing significantly lowered the protein expressions of Beclin and LC3A/B in 786-O cells. CONCLUSIONS Interference of BIRC6 mediated by siRNA can inhibit autophagy and promote 5-FU-induced apoptosis to enhance the sensitivity of 786-O cells to 5-FU.

Non-coding RNAs play an important role in the pathogenesis of prostate cancer (PC). This study aims to characterize the role of GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms in the pathogenesis of PC. Both INS allele of GAS5 rs145204276 and A allele of HOTAIR rs4759314 were identified to increase the survival of PC patients. And patients carrying DEL/DEL + AG genotypes tend to present higher levels of HMGB1, GAS5, HOTAIR and lower levels of miR-1284 and miR-22. In addition, the transcription activity of GAS5 promoter was increased by the deletion allele of rs145204276 polymorphism, while the G allele of rs4759314 polymorphism increased the transcription activity of HOTAIR promoter. GAS5 and HOTAIR could bind to miR-1284 and miR-22, respectively, while miR-1284 and miR-22 could bind to the 3 ' UTR of HMGB1. Compared with the control group, the expressions of miR-1284 or miR-22 were decreased with the presence of GAS5 or HOTAIR, and the expression of HMGB1 was the highest in the GAS5 + HOTAIR group. In summary, the findings of this study demonstrated that both GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms could affect the prognosis of PC by modulating the expression of HMGB1 via modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways.

BACKGROUND:The treatment of ketamine-induced bladder contractures remains poorly studied. We therefore evaluated the efficacy of cystectasia with a sodium hyaluronate balanced solution in this kind of bladder contracture.METHODS:Eighteen patients presenting with ketamine-induced bladder contracture between July 2010 and February 2018 were selected and analysed. Ketamine was discontinued in all patients, who were then treated with weekly cystectasia (0.09% sodium hyaluronate balanced solution) 3 times. The volume of the first perfusion was twice the preoperatively measured bladder capacity, and the volume of the subsequent two perfusions was increased by 100 mL each time. The Pelvic Pain and Urgency/Frequency (PUF) symptom score, O'Leary-Sant Interstitial Cystitis (IC) Symptom Index (ICSI), IC Problem Index (ICPI), Quality of Life (QOL) score, and bladder capacity were recorded before surgery and 3 and 12 months after the 3rd expansion.RESULTS:No significant complications were observed during the 3 expansions. Fourteen patients completed the full follow-up schedule. Preoperatively and at the 3- and 12-month follow-up evaluations performed after the 3rd expansion, the PUF symptom scores were 20.4±3.6, 11.5±3.1, and 13.2±3.3, respectively; the mean ICSI was 13.6±2.8, 7.7±2.3, and 8.2±2.5, respectively; the mean ICPI was 10.6±2.6, 7.3±2.1, and 7.7±2.5, respectively; and the mean QOL scores were 6.0±0, 2.1±0.5, and 2.7±0.8, respectively; and the mean bladder catheter volume was 83±27, 234±56, and 228±52 mL, respectively. There were significant differences between all preoperative and postoperative values.CONCLUSIONS:Cystectasia with a sodium hyaluronate balanced solution is an effective treatment modality for ketamine-induced bladder contracture.

Lactate dehydrogenase isozyme (LDH) is a tetramer constituted of two isoforms, LDHA and LDHB, the expression of which is associated with cell metabolism and cancer progression. Our previous study reveals that CC-chemokine ligand-18 (CCL18) is involved in progression of prostate cancer (PCa).This study aims to investigate how CCL18 regulates LDH isoform expression, and therefore, contributes to PCa progression. The data revealed that the expression of LDHA was upregulated and LDHB was downregulated in PCa cells by CCL18 at both messenger RNA and protein levels. The depletion of CCR8 reduced the ability of CCL18 to promote the proliferation, migration, and lactate production of PCa cells. Depletion of a CCR8 regulated transcription factor, ARNT, significantly reduced the expression of LDHA. In addition, The Cancer Genome Atlas dataset analyses revealed a positive correlation between CCR8 and ARNT expression. Two dimension difference gel electrophoresis revealed that the LDHA/LDHB ratio was increased in the prostatic fluid of patients with PCa and PCa tissues. Furthermore, increased LDHA/LDHB ratio was associated with poor clinical outcomes of patients with PCa. Together, our results indicate that the CCR8 pathway programs LDH isoform expression in an ARNT dependent manner and that the ratio of LDHA/LDHB has the potential to serve as biomarkers for PCa diagnosis and prognosis.

1 病例介绍 患者,女,51岁,因“反复胸闷,胸痛5年,加重头痛1个月”入住本院心内科.CT检查发现左肾积水后,患者转至泌尿外科.无腹胀、腹痛,无尿频、尿急、尿痛、排尿困难及尿流中断等,无烟酒嗜好,无手术史,无家族病史.查体:生命体征平稳,神清,心、肺未见异常,腹平软,全腹未扪及肿块,无压痛、反跳痛,双肾区无叩痛.入院后行尿常规检查,尿白细胞计数为87/μl,尿潜血阳性.血清肌酐79 μmol/L,血常规、肝功能及凝血参数均在正常范围.

Increasing evidence indicates that immunoglobulins are important for the regulation of various cancers including prostate cancer (PCa). However, the underlying mechanisms of IgG regulated PCa development remain to be further explored. Here, we demonstrated that IgG1 heavy chain (IGHG1) was increased in tissues from PCa patients. Inhibition of IGHG1 by antibody blocking or genetic knockdown suppressed cell growth and induced cell cycle arrest and ultimate apoptosis. Expression levels of c-Myc were positively correlated with the levels of IGHG1. Furthermore, MEK/ERK/c-Myc pathway lied downstream of IGHG1 in cultured prostate cancer cells. Inhibition of IGHG1 restrained the tumor growth in nude mice and inactivated MEK/ERK/c-Myc pathway both in vitro and in vivo. These findings suggest that IGHG1 play a crucial role during the development of prostate cancer and inhibition of IGHG1 may be a potential therapy in the treatment of PCa.

目的 探究雌激素受体α(ERα)、雌激素受体β(ERβ)、G蛋白偶联雌激素受体30(GPR30)及雄激素受体(AR)在人良性前列腺增生组织的表达及其意义.方法 取良性前列腺增生组织标本48例及膀胱癌根治术病理诊断为正常前列腺组织标本19例,利用RT-PCR及Western blotting检测两种前列腺组织中ERα、ERβ、GPR30、AR mRNA及蛋白表达水平.结果 与正常前列腺组织比较,良性前列腺增生组织ERα、AR mRNA及蛋白表达明显增加(P均<0.05),GPR30 mRNA及蛋白表达明显减少(P均<0.05),ERβmRNA及蛋白表达两者差异无统计学意义(P均>0.05).结论 性激素相关受体表达水平的紊乱可能是诱发良性前列腺增生的危险因素.

Upregulated gene 11 (URG11), a new gene upregulated by hepatitis B virus X protein, is involved in the development and progression of several tumors, including liver, stomach, lung, and colon cancers. However, the role of URG11 in prostate cancer remains yet to be elucidated. By determined expression in human prostate cancer tissues, URG11 was found significantly upregulated and positively correlated with the severity of prostate cancer, compared with that in benign prostatic hyperplasia tissues. Further, the mRNA and protein levels of URG11 were significantly upregulated in human prostate cancer cell lines (DU145, PC3, and LNCaP), compared with human prostate epithelial cell line (RWPE-1). Moreover, by the application of siRNA against URG11, the proliferation, migration, and invasion of prostate cancer cells were markedly inhibited. Genetic knockdown of URG11 also induced cell cycle arrest at G1/S phase, induced apoptosis, and decreased the expression level ofβ-catenin in prostate cancer cells. Overexpression of URG11 promoted the expression ofβ-catenin, the growth, the migration, and invasion ability of prostate cancer cells. Taken together, this study reveals that URG11 is critical for the proliferation, migration, and invasion in prostate cancer cells, providing the evidence of URG11 to be a novel potential therapeutic target of prostate cancer.