Small RNA-induced INTS6 gene up-regulation suppresses castration-resistant prostate cancer cells by regulating ß-catenin signaling.

Small RNAs play an important role in gene regulatory networks. The gene suppressive effect of small RNAs was previously the dominant focus of studies, but during the recent decade, small RNA-induced gene activation has been reported and has become a notable gene manipulation technique. In this study, a putative tumor suppressor, INTS6, was activated by introducing a promoter-targeted small RNA (dsRNA-915) into castration-resistant prostate cancer (CRPC) cells. Unique dynamics associated with the gene upregulation phenomenon was observed. Following gene activation, cell proliferation and motility were suppressed in vitro. Downregulation of Wnt/ß-catenin signaling was observed during the activation period, and the impairment of ß-catenin degradation reversed the tumor suppressor effects of INTS6. These results suggest the potential application of small activating RNAs in targeted gene therapy for CRPC.

MiR-124 suppresses cell motility and adhesion by targeting talin 1 in prostate cancer cells.

BACKGROUND: MicroRNA is a type of endogenous non-coding RNA implicated in various cellular processes, and has been intensely investigated in the field of cancer research for many years. Here, we investigated the functions and mechanisms of miR-124 in prostate cancer, which is a putative tumor suppressor reported in many carcinomas. METHODS: Using bioinformatics, talin 1 was indicated as a potential target of miR-124. We examined the expression levels of miR-124 and talin 1 in tissue specimens and cell lines. To explore the relationship between miR-124 and talin 1, miR-124 mimics, miR-124 inhibitors, and talin 1 small interfering RNA (siRNA) were transiently transfected into cancer cell lines, followed by analysis using luciferase reporter assays. Next, to investigate the functions of miR-124 in prostate cancer, we performed cell attachment, migration, and invasion assays. A rescue experiment was also conducted to demonstrate whether miR-124 suppressed cell adhesion and motility by targeting talin 1. Finally, we examined the related signaling pathways of miR-124 and talin 1. RESULTS: MiR-124 was down-regulated in prostate cancer specimens and cell lines, while talin 1 was over-expressed in prostate cancer specimens and cell lines. These results showed an inverse correlation of miR-124 and talin 1 expression. Similar to talin 1 siRNA, overexpression of miR-124 by transient transfection of mimics led to a significant decrease in talin 1 levels. Luciferase report assays showed that the seed sequence of the talin 1 3'-untranslated region was a target of miR-124. Functional investigations revealed anti-attachment, anti-migration, and invasion-promoting effects of miR-124 in prostate cancer cells. The rescue experiment confirmed that miR-124 exerted its biological functions by targeting talin 1. Finally, we found that miR-124 and talin 1 impaired cellular adhesion and motility through integrins and the focal adhesion kinase/Akt pathway. CONCLUSIONS: Our study demonstrated biological roles and the related mechanism of miR-124 in prostate cancer. The results indicate that talin 1 is very likely a novel player in the anti-metastatic signaling network of miR-124. By down-regulation of talin 1, miR-124 impairs the adhesion, migration, and invasion of prostate cancer cells.

The iatrogenic injury of double vena cava due to misdiagnosis during the radical nephroureterectomy and cystectomy.

Double inferior vena cava (d-IVC) is a subtype of vascular anomaly that rarely needs treatment. Here, we present a rare case of d-IVC accompanied with concurrent renal pelvis and bladder carcinoma. Due to misdiagnosis, the anomalous left inferior vena cava (IVC) entering the left renal vein was mistaken as the gonadal vein and was then severed during the radical nephroureterectomy. Fortunately, the injured left IVC was recognized correctly during the following cystectomy. The vascular reconstruction operation was performed to recanalize the left iliac veins by anastomosing the ligated vascular stump to the right IVC in an 'end-to-side' way. During the hospitalization, the patient was treated with 'low molecular weight heparin' and then warfarin to ensure an ideal international normalized ratio. He recovered well from the surgery. A meticulous and comprehensive analysis of radiographic imaging is critical to avoid misdiagnosis of d-IVC.

Primary ectopic atypical meningioma in the renal hilum: a case report.

BACKGROUND: Primary ectopic atypical meningioma involving the renal hilum is rare. This is, to our knowledge, only the second case report of a primary retroperitoneal meningioma and the first case of an atypical subtype in this location. CASE PRESENTATION: A 53-year-old Han Chinese man presented with a 2-year history of left-side flank pain. An oval-shaped retroperitoneal mass was found in the left renal hilum on computed tomography, which was resected en bloc along with the kidney via laparotomy. According to the World Health Organization criteria, the tumor was histopathologically classified as a meningioma (Grade II, atypical). Five years later, the tumor recurred at the primary site with a similar histopathology. The patient received palliative resection, followed by radiotherapy (4500 cGy in 25 fractions). No relapse was found at 6-month follow-up. CONCLUSION: We describe the clinical, radiographic and histopathological features of an unusual case of aggressive ectopic meningioma in the renal hilum. The patient presented with a massive retroperitoneal tumor without primary cerebral or secondary metastatic lesions; the preoperative diagnosis was naturally confined to the common retroperitoneal malignancies. This case is of interest to oncologists, because of both its rare location and aggressiveness; it not only enriched the spectrum of primary ectopic meningioma, but also reminded us of potential recurrence of an atypical meningioma. This case raises the issue of the etiology of such a rare tumor that needs further investigation, and more importantly demands long-term follow-up result.

No association between tea consumption and risk of renal cell carcinoma: a meta-analysis of epidemiological studies.

OBJECTIVE: To evaluate the association between tea consumption and the risk of renal cell carcinoma. METHODS: We searched PubMed,Web of Science and Scopus between 1970 and November 2012. Two evaluators independently reviewed and selected articles based on predetermined selection criteria. RESULTS: Twelve epidemiological studies (ten case-control studies and two cohort studies) were included in the final analysis. In a meta-analysis of all included studies, when compared with the lowest level of tea consumption, the overall relative risk (RR) of renal cell carcinoma for the highest level of tea consumption was 1.03 (95% confidence interval [CI] 0.89-1.21). In subgroup meta-analyses by study design, there was no significant association between tea consumption and renal cell carcinoma risk in ten case-control studies using adjusted data (RR=1.08, 95% CI 0.84-1.40). Furthermore, there was no significant association in two cohort studies using adjusted data (RR=0.95, 95% CI 0.81-1.12). CONCLUSION: Our findings do not support the conclusion that tea consumption is related to decreased risk of renal cell carcinoma. Further prospective cohort studies are required.

Genetic polymorphisms of glutathione S-transferase M1 and prostate cancer risk in Asians: a meta-analysis of 18 studies.

BACKGROUND: Many studies have investigated associations between the glutathione S-transferase M1 (GSTM1) null polymorphism and risk of prostate cancer, but the impact of GSTM1 in people who live in Asian countries is still unclear owing to inconsistencies across results. METHODS: We searched the PubMed, Web of Science, Scopus, Ovid and CNKI databases for studies of associations between the GSTM1 null genotype and risk of prostate cancer in people who live in Asian countries, and estimated summary odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: A total of 18 case-control studies with 2,172 cases and 3,258 controls were included in this meta-analysis, which showed the GSTM1 null genotype to be significantly associated with increased risk of prostate cancer in people who live in Asian countries (random-effects OR=1.74, 95% CI1.44-2.09, P<0.001). Similar results were found in East Asians (OR=1.41; 95% CI: 1.12-1.78; P=0.004) and Caucasians in Asia (OR=2.19; 95% CI: 1.85-2.60; P<0.001). No evidence of publication bias was observed. CONCLUSIONS: This meta- analysis of available data suggested that the GSTM1 null genotype does contribute to increased risk of prostate cancer in people who live in Asian countries.

MicroRNA-449a acts as a tumor suppressor in human bladder cancer through the regulation of pocket proteins.

Frequent downregulation of microRNA-449a (miR-449a) was detected in 14 human bladder cancer tissues. The restoration of miR-449a inhibited cell growth and induced G1-phase arrest in T24 and 5637 human bladder cancer cells. CDK6 and CDC25a were downregulated after miR-449a treatment, resulting in the functional accumulation of the pocket proteins Rb and p130. The growth of T24 tumor xenografts was suppressed by exogenous miR-449a, and the nuclear proliferation antigen Ki-67 was downregulated in miR-449a-treated tumors. These results suggest a tumor-suppressive role for miR-449a in human bladder cancer.

Prostate cancer risk in relation to a single nucleotide polymorphism in the insulin-like growth factor-binding protein-3 (IGFBP3) gene: a meta-analysis.

Insulin-like growth factor-binding protein-3 (IGFBP3) has been identified as a putative tumor suppressor with multifunctional roles in the IGF axis. Recently, there have been a growing body of studies investigating the relation between the IGFBP3 A-202C polymorphism, circulating IGFBP3 and prostate cancer risk, but their outcomes varied leading to controversy. Hence, it is necessary to perform a meta-analysis covering all eligible studies to shed a light on the association of IGFBP3 A-202C and cancer risk. Finally, we included a total of 11 relevant articles between 2003 and 2010 covering 14 case-control studies including 9,238 cases and 8,741 controls for our analysis. Our results showed that A-202C was a marginal risk factor of prostate cancer (allele contrast: OR=1.08, 95% CI :1.01-1.16; dominant model: OR=1.11, 95% CI :1.01-1.22; heterozygote codominant model: OR=1.11, 95% CI :1.03-1.18; homozygote contrast: OR=1.19, 95% CI :1.03-1.37). Stratification analysis revealed that sample size and control source were two major heterogeneous meta-factors especially in the recessive model (source: Population-based control group :p=0.30,I2=16.7%, Hospital-based control group: p=0.20, I2=30.3%; sample size: Small: p=0.22,I2= 32.8%, Medium: p=0.09,I2= 48%, Large p=0.60,I2=0.0%); However, contrary to previous findings, no significance was found in racial subgroups. No significant publication bias was found in our analysis. Considering the robustness of the results and the discrepancy among some studies, there might be some unsolved confounding factors, and further more critical large studies are needed for confirmation.

Angiotensin-converting enzyme insertion/deletion polymorphism and the risk of prostate cancer in the Han population of China.

As a main effector in the renin-angiotensin system, the angiotensin II plays a critical role in cell proliferation and angiogenesis. The change between angiotensin II and its precursor is conducted by the angiotensin-converting enzyme. The association between angiotensin-converting enzyme insertion/deletion polymorphism and the activity of angiotensin-converting enzyme was testified. Furthermore, previous researches proved the association between angiotensin-converting enzyme activity and the risk of prostate cancer. Therefore, we conducted a case-control study in the Han population of China to elaborate the relation between the angiotensin-converting enzyme insertion/deletion polymorphism and prostate cancer. DNA was extracted from blood samples collected from 189 pathologically diagnosed prostate cancer patients and 290 cancer-free subjects. The angiotensin-converting enzyme insertion/deletion genotype was determined by polymerase chain reaction analysis. Stratified analyses on age (<71 or ≥ 71), cancer stage (localized or advanced), Gleason score (<7 or ≥ 7) and PSA level (<20 ng/ml or ≥ 20 ng/ml) were performed. We found the II genotype (OR = 0.304 95%CI (0.180,0.515), P < 0.001) and I allele (OR = 0.547 95%CI(0.421,0.711), P < 0.001) were associated with a decreased risk of prostate cancer compared with the DD genotype and D allele. The DD genotype was related to patients with aggressive stage of prostate cancer (OR = 2.214 95%CI(1.169, 4.194), P = 0.014) and patients diagnosed of prostate cancer at a relatively early age (OR = 0.513 95%CI(0.272, 0.965), P = 0.037). The results of our experiment supported the hypothesis that the angiotensin-converting enzyme insertion/deletion polymorphism, a potential risk factor in carcinogenesis, played an important role in the Han population of China.