Inhibition of miR-34a-5p can rescue disruption of the p53-DAPK axis to suppress progression of clear cell renal cell carcinoma.

DAPK, a transcriptional target of the p53 protein, has long been characterized as a tumor suppressor that acts as a negative regulator in multiple cellular processes. However, increasing studies have suggested that the role of DAPK may vary depending on cell type and cellular context. Thus far, the expression and function of DAPK in clear cell renal cell carcinoma (ccRCC) remain ambiguous. Since ccRCC behaves in an atypical way with respect to p53, whether the p53-DAPK axis functions normally in ccRCC is also an intriguing question. Here, tissue specimens from 61 ccRCC patients were examined for DAPK expression. Functional studies regarding apoptosis, growth, and migration were used to determine the role of DAPK in renal cancer cells. The validity of the p53-DAPK axis in ccRCC was also determined. Our study identified DAPK as a negative regulator of ccRCC, and its expression was reduced in certain subgroups. However, the p53-DAPK axis was disrupted due to upregulation of miR-34a-5p under stressed conditions. miR-34a-5p was identified as a novel repressor of DAPK acting downstream of p53. Inhibition of miR-34a-5p can correct the p53-DAPK axis disruption by upregulating DAPK protein and may have potential to be used as a therapeutic target to improve outcomes for ccRCC patients.

Overexpression of SNHG12 regulates the viability and invasion of renal cell carcinoma cells through modulation of HIF1α.

BACKGROUND: Cumulative evidences demonstrated the aberrant overexpression of Small Nucleolar RNA Host Gene 12 (SNHG12) in diverse human cancer. However, the expression status and involvement of SNHG12 in renal cell carcinoma is still elusive. METHODS: The expression of SNHG12 was determined by q-PCR. The transcriptional regulation was interrogated by luciferase reporter assay. Cell viability was measured with CCK-8 kit. The anchorage-independent was evaluated by soft agar assay. Cell apoptosis was analyzed by Annexin V/7-AAD double staining. The migration and invasion were determined by trans-well assay and wound scratch closure. The in vivo tumor growth was monitored in xenograft mice model. Protein expression was quantified by immunoblotting. RESULTS: SNHG12 was aberrantly up-regulated in renal carcinoma both in vivo and in vitro. High expression of SNHG12 associated with poor prognosis. Deficiency of SNHG12 significantly suppressed cell viability, anchorage-independent growth and induced apoptosis. In addition, SNHG12 silencing inhibited migrative and invasive in vitro and xenograft tumor growth in vivo. Mechanistically, SNHG12 modulated HIF1α expression via competing with miR-199a-5p, which consequently contributed to its oncogenic potential. MiR-199a-5p inhibition severely compromised SNHG12 silencing-elicited tumor repressive effects. CONCLUSION: Our data uncovered a crucial role of SNHG12-miR-199a-5p-HIF1α axis in human renal cancer.

miR-19 promotes the proliferation of clear cell renal cell carcinoma by targeting the FRK-PTEN axis.

BACKGROUND: The non-receptor tyrosine kinase Fyn-related kinase (FRK) has been reported to affect cell proliferation in several cancer types. However, its effect on the proliferation of clear cell renal cell carcinoma (ccRCC) remains largely unknown. PURPOSE: The objective of this study was to investigate the expression pattern and function of FRK in ccRCC. We further determined how FRK interacted with other molecules to regulate ccRCC proliferation. PATIENTS AND METHODS: The expression of FRK in ccRCC samples and paired normal renal tissues from 30 patients were analyzed by immunoblotting, immunohistochemistry and quantitative PCR. Then the role of FRK in ccRCC proliferation was analyzed by Cell Counting Kit-8, colony formation assay and EdU incorporation assay. In addition, the miRNA targeting FRK was predicted through a bioinformatic approach and validated by quantitative PCR, immunoblotting and luciferase reporter assay. Finally, the underlying mechanism of FRK regulation of ccRCC proliferation was also determined. RESULTS: Low expression of FRK was detected in ccRCC samples and predicted poor survival for ccRCC patients. FRK inhibited the proliferation of ccRCC cells via phosphorylating downstream PTEN. miR-19 was identified as a novel suppressor of FRK in renal cancer cells and it promoted the proliferation of ccRCC by inhibiting the FRK-PTEN axis. CONCLUSION: Our results unravel a new regulatory mechanism involved in ccRCC proliferation and may be useful in the identification of therapeutic targets for ccRCC.

[Effects of long non-coding RNA RP1-90L14.1 on the biological behaviors of cancer prostate LNCaP cells and its regulating mechanisms].

OBJECTIVE: To investigate the effects of long non-coding RNA RP1-90L14.1 on the proliferation, migration and invasion of prostate cancer LNCaP cells and the expressions of GRIN2A and BACE2. METHODS: Using RT-PCR, we detected the expression of RP1-90L14.1 in LNCaP and LNCaP-AI cells, transiently transfected the RP1-90L14.1 overexpression plasmid (the RP1-90L14.1 group) and vector plasmid (the LNCaP-NC group) into the LNCaP cells, and cultured the two groups of cells with ordinary medium and phenol red-free activated carbon adsorption medium (PRF-ACA). Then we examined the proliferation, migration and invasiveness of the cells by CCK-8 and Transwell, and determined the mRNA and protein expressions of GRIN2A and BACE2 by RT-PCR and Western blot. RESULTS: The expression of RP1-90L14.1 was significantly higher in the LNCaP-AI than in the LNCaP cells (8.49 ± 0.43 vs 2.53 ± 0.95, P < 0.05), and so was that of LNCaP-RP1-90L14.1 in the RP1-90L14.1 than in the LNCaP-NC group after transfection (0.71 ± 0.22 vs 0.02 ± 0.01, P < 0.05). The optical densities (OD) of the cells were 51.95% and 50.69% higher in the RP1-90L14.1 than in the LNCaP-NC group after 72 hours of culture with ordinary medium and phenol red-free ACA (1.22 ± 0.08 vs 0.08 ± 0.05, P < 0.05; 0.79 ± 0.02 vs 0.53 ± 0.05, P < 0.05), and 51.72% and 60.23% higher in the former than in the latter after 96 hours (1.72 ± 0.07 vs 1.13 ± 0.05, P < 0.05; 1.18 ± 0.05 vs 0.73 ± 0.08, P < 0.05). The numbers of the migrating cells cultured with common medium and PRF-ACA were markedly higher in the RP1-90L14.1 than in the LNCaP-NC group after transfection (682.0 ± 42.7 vs 422.0 ± 37.1, P < 0.05; 419.0 ± 42.9 vs 251.0 ± 25.9, P < 0.05), and so were those of the invading cells (507.0 ± 22.2 vs 274.0 ± 19.6, P < 0.05; 352.0 ± 14.1 vs 216.0 ± 14.3, P < 0.05). Statistically significant differences were observed between the RP1-90L14.1 and LNCaP-NC groups in the mRNA and protein expressions of GRIN2A (5.13 ± 0.89 vs 2.09 ± 0.54, P < 0.05; 5.88 ± 0.29 vs 2.03 ± 0.22, P < 0.05) and BACE2 (5.82 ± 0.50 vs 2.53 ± 0.30, P < 0.05; 4.89 ± 0.19 vs 3.37 ± 0.13, P < 0.05). CONCLUSIONS: 　lncRNA RP1-90L14.1 may play important roles in the proliferation, migration and invasiveness of prostate cancer cells. RP1-90L14.1 can promote the expressions of GRIN2A and BACE2 and may have an endogenous competitive relation with GRIN2A and BACE2.

Positive factors associated with quality of life among Chinese patients with renal carcinoma: a cross-sectional study.

Quality of life and positive psychological variables has become a focus of concern in patients with renal carcinoma. However, the integrative effects of positive psychological variables on the illness have seldom been reported. The aims of this study were to evaluate the quality of life and the integrative effects of hope, resilience and optimism on the quality of life among Chinese renal carcinoma patients. A cross-sectional study was conducted at the First Hospital of China Medical University. 284 participants completed questionnaires consisting of demographic and clinical characteristics, EORTC QLQ-C30, Adult Hope Scale, Resilience Scale-14 and Life Orientation Scale-Revised from July 2013 to July 2014. Pearson's correlation and hierarchical regression analyses were performed to explore the effects of related factors. Hope, resilience and optimism were significantly associated with quality of life. Hierarchical regression analyses indicated that hope, resilience and optimism as a whole accounted for 9.8, 24.4 and 21.9% of the variance in the global health status, functioning status and symptom status, respectively. The low level of quality of life for Chinese renal carcinoma patients should receive more attention from Chinese medical institutions. Psychological interventions to increase hope, resilience and optimism may be essential to enhancing the quality of life of Chinese cancer patients.

TRPM7 is overexpressed in bladder cancer and promotes proliferation, migration, invasion and tumor growth.

Recent findings suggest that the melastatin transient receptor potential channel 7 (TRPM7) is overexpressed in many types of cancers and is involved in tumorigenesis. However, its expression pattern and the potential role in bladder cancer remain unclear. The aim of the present study was to investigate the expression status of TRPM7 and its relationship with the development of bladder cancer. In the present study, we observed that the expression of TRPM7 was significantly elevated in bladder cancer tissues compared with that noted in the adjacent non-tumor tissues. Furthermore, increased TRPM7 expression was significantly associated with recurrence, metastasis and prognosis. In addition, after knockdown of the expression of TRPM7 by siRNA, the proliferation and the motility of T24 and 5637 cells were obviously inhibited, and downregulation of TRPM7 was found to play an important role in bladder cancer cell apoptosis. In conclusion, our findings suggest that TRPM7 plays an important role in bladder cancer, and TRPM7 may serve as a potentially unfavorable factor and novel target for human bladder cancer.

MiR-378 suppresses prostate cancer cell growth through downregulation of MAPK1 in vitro and in vivo.

Prostate cancer is one of the biggest health problems for the aging male. To the present, the roles of dysregulated microRNAs in prostate cancer are still unclear. Here, we evaluated the anti-proliferative role of miR-378 in prostate cancer. And, we found that the expression of miR-378 was significantly downregulated in clinical prostate cancer tissues. In vitro assay suggested that overexpression of miR-378-suppressed prostate cancer cell migration and invasion promoted cell apoptosis. Furthermore, we identified and validated MAPK1 as a direct target of miR-378. Ectopic expression of MAPK1 rescues miR-378-suppressed cell migration and invasion. In vivo assay demonstrated that the stably miR-378-overexpressed prostate cancer cells displayed a significantly reduction in tumor growth. Taken together, our data suggested that miR-378 may act as a potential therapeutic target against human prostate cancer.

MiR-345 suppresses proliferation, migration and invasion by targeting Smad1 in human prostate cancer.

INTRODUCTION: The roles of dysregulated microRNAs in prostate cancer metastasis are still unknown. In this study, we found that the expression of miR-345 was significantly downregulated in prostate cancer and clinical prostate cancer tissues. MATERIALS, METHODS AND RESULTS: Overexpression of miR-345 in prostate cancer cells suppressed proliferation, migration and invasion. Using nude mice model, we revealed that miR-345 inhibits the growth of prostate cancer cells in vivo and in vitro. Furthermore, we identified and validated Smad1 as a direct target of miR-345. Ectopic expression of Smad1 without its 3'-UTR rescued miR-345-induced cell migration and invasion inhibition. CONCLUSION: Taken together, our data suggest that miR-345 exerts a suppressive effect on prostate cancer proliferation, invasion and migration through downregulation of Smad1.

Aplasia Ras homolog member I expression induces apoptosis in renal cancer cells via the ß-catenin signaling pathway.

In numerous types of cancer, the Ras-associated tumor suppressor gene aplasia Ras homolog member I (ARHI), is downregulated. However, the function of ARHI in renal cancer remains to be elucidated. The present study investigated whether the suppressor gene ARHI influenced the growth of renal cancer cell lines and aimed to elucidate its mechanism of action, using the techniques of cell biology and molecular pathology. To the best of our knowledge, the present study was the first to determine the effects of ARHI on human renal cancer cells in vivo and in vitro. It was demonstrated that ARHI exhibited a tumor suppressor function in OS-RC-2 cells and acted via the ß-catenin signaling pathway. It was additionally confirmed that the levels of ARHI messenger RNA and protein in renal cancer tissues were lower than those in matched normal tissues. These results provided a novel insight into the possible therapeutic applications of ARHI in renal cancer.

PKC α regulates netrin-1/UNC5B-mediated survival pathway in bladder cancer.

BACKGROUND: Netrin-1 and its receptor UNC5B play important roles in angiogenesis, embryonic development, cancer and inflammation. However, their expression patttern and biological roles in bladder cancer have not been well characterized. The present study aims to investigating the clinical significance of PKC α, netrin-1 and UNC5B in bladder cancer as well as their association with malignant biological behavior of cancer cells. METHODS: Netrin-1 and UNC5B expression was examined in 120 bladder cancer specimens using immunohistochemistry and in 40 fresh cancer tissues by western blot. Immunofluorescence was performed in cancer cell lines. PKC α agonist PMA and PKC siRNA was employed in bladder cancer cells. CCK-8, wound healing assays and flow cytometry analysis were used to examine cell proliferation, migration and cell cycle, respectively. RESULTS: Netrin-1 expression was positively correlated with histological grade, T stage, metastasis and poor prognosis in bladder cancer tissues. Immunofluorescence showed elevated netrin-1 and decreased UNC5B expression in bladder cancer cells compared with normal bladder cell line. Furthermore, cell proliferation, migration and cell cycle progression were promoted with PMA treatment while inhibited by calphostin C. In addition, PMA treatment could induce while calphostin C reduce netrin-1 expression in bladder cancer cells. CONCLUSIONS: The present study identified netrin-1/UNC5B, which could be regulated by PKC signaling, was important mediators of bladder cancer progression.

Relationships between CYP1A1 genetic polymorphisms and bladder cancer risk: a meta-analysis.

This meta-analysis aims at evaluating the relationships between CYP1A1 genetic polymorphisms and bladder cancer risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched from inception through November 1st, 2013 without language restrictions. Meta-analysis was conducted with the use of the STATA 12.0 software. The relationships were evaluated by calculating the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). Eight case-control studies with a total of 2120 bladder cancer patients and 2061 healthy subjects met the inclusion criteria. Ten common polymorphisms in the CYP1A1 gene were assessed. The results of our meta-analysis suggested that CYP1A1 genetic polymorphisms might be strongly correlated with an increased risk of bladder cancer (allele model: OR=1.23, 95%CI=1.08-1.39, p=0.001; dominant model: OR=1.25, 95%CI=1.07-1.46, p=0.005; respectively), especially for 11599G>C, 2455A>G, 3810T>C, and 113T>C polymorphisms. A subgroup analysis was done to investigate the effect of ethnicity on an individual's risk of bladder cancer. Our results revealed positive significant correlations between CYP1A1 genetic polymorphisms and an increased risk of bladder cancer among Asians (allele model: OR=1.33, 95%CI=1.08-1.65, p=0.009; dominant model: OR=1.37, 95%CI=1.02-1.85, p=0.034; respectively), but not among Caucasians (all p<0.05). Our findings provide convincing evidence that CYP1A1 genetic polymorphisms may contribute to susceptibility to bladder cancer, especially for 11599G>C, 2455A>G, 3810T>C, and 113T>C polymorphisms among Asians.

Role of CDH1 promoter polymorphism and DNA methylation in bladder carcinogenesis: a meta-analysis.

Increasing scientific evidences suggest that CDH1 gene promoter polymorphism and DNA methylation may contribute to the development and progression of bladder cancer, but many existing studies have yielded inconclusive results. This meta-analysis aims to assess the role of CDH1 gene promoter polymorphism and methylation in bladder carcinogenesis. An extensive literature search for relevant studies was conducted in PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through April 1, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude odds ratio with 95% confidence interval was calculated. Fifteen studies were included in this meta-analysis with a total of 824 bladder cancer patients and 818 healthy controls being assessed. Our meta-analysis revealed that the A variant of CDH1 -160C/A polymorphism was associated with an increased risk of bladder cancer. Further analysis by pathological subtype indicated that patients with invasive carcinoma had a higher frequency of CDH1 -160A variant than those with superficial carcinoma. We analyzed the methylation frequency of CDH1 gene in 608 bladder cancer samples and 338 normal bladder samples. Our data strongly suggest that the CDH1 promoter methylation frequencies in bladder cancer tissues were greater than those in normal control tissues. In conclusion, our meta-analysis indicates that promoter polymorphism and methylation of CDH1 gene may be involved in the development and progression of bladder cancer. CDH1 gene promoter polymorphism and methylation might be promising biomarkers for the diagnosis and prognosis of bladder cancer.

[Clinical efficacy of daily low-dose tadalafil on erectile dysfunction-no sexual life].

OBJECTIVE: Erectile dysfunction-no sexual life (ED-NS) is defined as the inability to have enough penile erection hardness and duration so as to have enough confidence in attempting sexual intercourse for more than six months. This study was to investigate the effect of daily low-dose tadalafil on ED-NS. METHODS: We treated 35 ED-NS patients aged 17-35 (25.9 +/- 3.9) years with oral tadalafil at 5 mg qd for 3 months and followed them up for another 3 months after drug withdrawal. We obtained the scores of the patients on Self-estimation Index of Erectile Function-No Sexual Life (SIEF-NS) and compared them before and after medication and at 3 months after drug withdrawal. RESULTS: The patients' SIEF-NS scores were 43.2 +/- 7.1 after medication and 42.1 +/- 7.4 at 3 months after drug withdrawal, both significantly higher than 21.2 +/- 5.9 before treatment (P < 0.05), though there was no significant difference between the former two scores (P > 0.05). CONCLUSION: Daily medication of low-dose tadalafil can significantly improve the erectile function of the patients with ED-NS.

Interactional expression of netrin-1 and its dependence receptor UNC5B in prostate carcinoma.

Acting via its receptor UNC5B, netrin-1, one of the major neuronal guidance cues, plays an important role in angiogenesis, neurogenesis, tissue morphogenesis, embryonic development, cancer, inflammation, and various pathologies. However, its role has not been reported in prostate carcinoma. To investigate the association of netrin-1 and UNC5B expression with prostate carcinoma, several human prostate carcinoma cell lines were cultured and the expression levels of netrin-1 and UNC5B were determined by real-time PCR and Western blot. Calphostin C, (the inhibitor of PKC α) and phorbol-12-myristate 13-acetate-PMA (the agonist of PKC α) were used to treat the prostate carcinoma cells, and the cell proliferation and invasion abilities were measured by CCK-8 and wound-healing assays. Proliferation of DU145 cells was affected by the recruitment of PMA and calphostin C in a dose-dependent manner. By immunofluorescence, we identified the localization of netrin-1 and UNC5B in prostate carcinoma cell lines (DU145, 22RV1, PC3, PC3M, and RWEP) and found that netrin-1 was highly expressed in the nucleolus but there was no expression of UNC5B. The co-localization expression of PKC α and UNC5B was confirmed by the confocal immunofluorescence. Higher netrin-1 and lower UNC5B expression in all prostate carcinoma cell lines indicated that netrin-1 and UNC5B could be used to predict metastasis.

MicroRNA-141 is downregulated in human renal cell carcinoma and regulates cell survival by targeting CDC25B.

UNLABELLED: BACKGROUNDOBJECTIVE: MicroRNAs (miRNAs) are small noncoding RNAs (ribonucleic acids), approximately 22 nucleotides in length, that function as regulators of gene expression. Dysregulation of miRNAs has been associated with the initiation and progression of oncogenesis in humans. The cell division cycle (CDC)25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. METHODS: Using miRNA target prediction software, we found that miR-141 could target the 3' untranslated region (3'UTR) sequence of CDC25B. To shed light on the role of miR-141 in renal cell carcinogenesis, the expression of miR-141 was examined by real-time polymerase chain reaction (RT-PCR) in renal cell carcinoma and normal tissues. The impact of miR-141 re-expression on 769-P cells was analyzed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony-forming assay. A luciferase reporter assay was applied to prove the functionality of the miR-141 binding site. RESULTS: miR-141 is significantly downregulated in renal cell carcinoma. miR-141 re-expression suppressed cell growth in 769-P cells. Luciferase expression from a reporter vector containing the CDC25B-3'UTR was decreased when this construct was transfected with miR-141 in 769-P cells. The overexpression of miR-141 suppressed the endogenous CDC25B protein level in 769-P cells. CONCLUSION: For the first time, we demonstrated that CDC25B is a direct target of miR-141 in renal cell carcinoma. The transcriptional loss of miR-141 and the resultant increase in CDC25B expression facilitates increased genomic instability at an early stage of renal cell carcinoma development.

Bcl-2 overexpression inhibits generation of intracellular reactive oxygen species and blocks adriamycin-induced apoptosis in bladder cancer cells.

Resistance to induction of apoptosis is a major obstacle for bladder cancer treatment. Bcl-2 is thought to be involved in anti-apoptotic signaling. In this study, we investigated the effect of Bcl-2 overexpression on apoptotic resistance and intracellular reactive oxygen species (ROS) generation in bladder cancer cells. A stable Bcl-2 overexpression cell line, BIU87-Bcl-2, was constructed from human bladder cancer cell line BIU87 by transfecting recombinant Bcl-2 [pcDNA3.1(+)-Bcl-2]. The sensitivity of transfected cells to adriamycin (ADR) was assessed by MTT assay. Apoptosis was examined by flow cytometry and acridine orange fluorescence staining. Intracellular ROS was determined using flow cytometry, and the activities of superoxide dismutase (SOD) and catalase (CAT) were also investigated by the xanthinoxidase and visible radiation methods using SOD and CAT detection kits. The susceptibility of BIU87-Bcl-2 cells to ADR treatment was significantly decreased as compared with control BIU87 cells. Enhanced expression of Bcl-2 inhibited intracellular ROS generation following ADR treatment. Moreover, the suppression of SOD and CAT activity induced by ADR treatment was blocked in the BIU87-Bcl-2 case but not in their parental cells. The overexpression of Bcl-2 renders human bladder cancer cells resistant to ADR-induced apoptosis and ROS might act as an important secondary messenger in this process.

The role of fascin in migration and invasion of urothelial carcinoma of the bladder.

INTRODUCTION: To investigate the roles of fascin in migration and invasiveness in bladder urothelial carcinoma. MATERIALS AND METHODS: Immunohistochemical detection of fascin in urothelial carcinoma samples and inhibition the expression of fascin in the urothelial carcinoma cell line were performed, then the differences in cell behaviors before and after silencing of the fascin gene were tested. RESULTS: In our study, we found that overexpression of fascin was more frequent in urothelial carcinoma tissues (p < 0.001). Fascin expression was positively correlated with histological grade (p = 0.024) and pT stage (p < 0.001). After transfection of fascin shRNA, the expressions of fascin in 5637 cells and BIU87 cells were efficiently decreased according to real-time RT-PCR and Western blot analysis. When fascin was inhibited, a significant decrease in migration and invasion, and increase in adhesion were observed in 5637 cells and BIU87 cells. However, there was no significant change in the proliferation of 5637 cells or BIU87 cells with or without inhibition of the fascin gene. CONCLUSIONS: Fascin expression can be used as a predictor for transformation and progression of urothelial carcinoma, and reduction of fascin levels may represent a novel therapeutic strategy for urothelial carcinoma of the bladder.

High FOXM1 expression was associated with bladder carcinogenesis.

The forkhead box M1 (FOXM1) transcription factor plays crucial roles in regulating the proliferation, differentiation, and transformation of cells. Overexpression of FOXM1 is associated with a variety of aggressive solid carcinomas, including bladder cancer. However, the precise role and molecular mechanism responsible for the aggressive action of FOXM1 in bladder cancer remain unclear. Real-time quantitative PCR, Western blot and immunohistochemistry were used to explore FoxM1 expression in bladder cancer cell lines, primary bladder cancer clinical specimens and normal bladder tissues. FoxM1 expression was knocked down by small interfering RNA (siRNA) in T24 cells; proliferation, migration and invasion were assayed. FoxM1 expression was up-regulated in the majority of the bladder cancer tissue specimens at both mRNA and protein levels. Immunohistochemistry analysis showed that FoxM1 expression was significantly correlated with TNM stage and histological grade, metastasis. Experimentally, we found that down-regulation of FoxM1 inhibited cell proliferation, migration and invasion. These results suggested that FOXM1 up-regulation was associated with poor prognosis in bladder cancer, and therefore it might act as a prognostic marker and a new potential target for bladder cancer treatment.

Clinical significance of UNC5B expression in bladder cancer.

UNC5B is a membrane-bound receptor of the neural guidance factor netrin-1 family, with important roles in angiogenesis, neurogenesis, embryonic development, cancer, inflammation and various pathologies. However, its effect on bladder cancer has not been reported. To investigate the association of UNC5B expression with bladder cancer prognosis, 100 cases of clinical bladder cancer and adjacent noncancerous tissue samples, and four bladder cancer cell lines were selected using RT-PCR, Western blot, immunofluorescence and immunohistochemistry to investigate differential expression and cellular positioning of UNC5B, and its relationship with clinicopathological parameters. In 72 % of cases, UNC5B was expressed in both bladder cancer and adjacent noncancerous tissue samples. Expression of UNC5B in bladder cancer tissues increased significantly as cancer stage increased (P < 0.05); UNC5B emerged more in bladder cancer cell lines with lower degrees of malignancy than those with higher degrees of malignancy; UNC5B expression in bladder cancer cells was significantly reduced compared to normal bladder cells (P < 0.05). UNC5B mRNA was down-expressed in about 28 % of bladder cancer tissues. Low UNC5B expression was an independent risk factor for postoperative recurrence in patients with different stages and grades bladder cancer. Furthermore, patients with lower UNC5B expression in tumors had significantly higher recurrence rate after curative surgery and poorer prognosis than those with higher UNC5B expression, suggesting that UNC5B could be used to predict prognosis and recurrence.

[Expressions of netrin-1 and UNC5B in prostate cancer and their clinical significance].

OBJECTIVE: To search for a new diagnostic biomarker for prostate cancer by comparing the differences in the expressions of netrin-1 and UNC5B in prostate cancer cells with different invasive abilities. METHODS: We examined the expressions of netrin-1 and UNC5B in five prostate cancer cell lines DU145, 22RV1, PC3, PC3M and RWPE-1 using RT-PCR and Western blot, and positioned the ligands netrin-1 and its receptor UNC5B in the prostate cancer cells by immunofluorescence. RESULTS: Both netrin-1 and UNC5B were expressed in the prostate cancer cells, and the expression of netrin-1 was significantly increased in highly invasive cells (P < 0.05), while that of UNC5B in RWPE-1 (normal) cells (P < 0.05). CONCLUSION: The expressions of netrin-1 and UNC5B are closely related to the infiltration and progression of prostate cancer, and expected to be as potential biomarkers for predicting the malignancy degree of prostate cancer.