MicroRNA-30c serves as an independent biochemical recurrence predictor and potential tumor suppressor for prostate cancer.

MicroRNA-30c (miR-30c) acts as a tumor suppressor or a tumor promoter in various human malignancies. However, the involvement of miR-30c in prostate cancer (PCa) is still unclear. The aim of this study was to investigate the molecular function and the clinical significance of miR-30c in PCa. Expression levels of miR-30c in PCa tissues and cells were detected by quantitative real-time-PCR (qRT-PCR). Additionally, the associations of miR-30c expression with clinicopathological features and prognosis in PCa patients were analyzed. The potential role of miR-30c in tumorigenesis of PCa cells was further evaluated by in vitro cell assays. MiR-30c was significantly down-regulated in PCa tissues and cells compared with the corresponding controls (P<0.05). In addition, the downregulation of miR-30c in PCa tissues was significantly associated with higher Gleason score (P=0.009), advanced pathological stage (P=0.016) and biochemical recurrence (P=0.034). Moreover, Kaplan-Meier survival analysis showed that the reduced expression of miR-30c was correlated with shorter biochemical recurrence-free survival (P=0.023). The multivariate analysis also identified miR-30c as an independent prognostic predictor for biochemical recurrence-free survival in patients with PCa. Furthermore, the enforced expression of miR-30c suppressed proliferation, migration and invasion of PCa cells in vitro. Our data indicated the involvement of miR-30c in PCa progression and suggested its potential role as an independent predictor of biochemical recurrence in PCa. On cellular level, miR-30c may function as a tumor suppressor for PCa cells by inhibiting tumor cell proliferation, migration and invasion.

Global analysis of the differentially expressed miRNAs of prostate cancer in Chinese patients.

BACKGROUND: Our recent study showed the global physiological function of the differentially expressed genes of prostate cancer in Chinese patients was different from that of other non-Chinese populations. microRNA are estimated to regulate the expression of greater than 60% of all protein-coding genes. To further investigate the global association between the transcript abundance of miRNAs and their target mRNAs in Chinese patients, we used microRNA microarray approach combined with bioinformatics and clinical-pathological assay to investigate the miRNA profile and evaluate the potential of miRNAs as diagnostic and prognostic markers in Chinese patients. RESULTS: A total of 28 miRNAs (fold change ≥ 1.5; P ≤ 0.05) were differentially expressed between tumor tissue and adjacent benign tissue of 4 prostate cancer patients.10 top Differentially expressed miRNAs were validated by qRT-PCR using all 20 tissue pairs. Compared to the miRNA profile of non-Chinese populations, the current study showed that miR-23b, miR-220, miR-221, miR-222, and miR-205 maybe common critical therapeutic targets in different populations. The integrated analysis for mRNA microarray and miRNA microarray showed the effects of specifically inhibiting and/or enhancing the function of miRNAs on the gene transcription level. The current studies also identified 15 specific expressed miRNAs in Chinese patients. The clinical feature statistics revealed that miR-374b and miR-19a have significant correlations with clinical-pathological features in Chinese patients. CONCLUSIONS: Our findings showed Chinese prostate cancer patients have a common and specific miRNA expression profile compared with non-Chinese populations. The miR-374b is down-regulated in prostate cancer tissue, and it can be identified as an independent predictor of biochemical recurrence-free survival.

Down-regulation of the ErbB3 binding protein 1 in human bladder cancer promotes tumor progression and cell proliferation.

The ErbB3 binding protein 1 (Ebp1) represents a downstream effector of the ErbB signaling network and has been demonstrated to be a potent tumor suppressor in various human malignancies, however, its involvement in human bladder cancer is still unclear.To investigate the clinical significance and potential role of ErbB3 binding protein 1 (Ebp1) in bladder cancer. Ebp1 expression at protein and gene levels in 52 surgically removed bladder cancer specimens as well as 21 adjacent normal bladder specimens were respectively detected by immunohistochemistry and qRT-PCR. The association of Ebp1 protein expression with the clinicopathological features of bladder cancer was also statistically analyzed. Its roles in bladder cancer cell line were further evaluated. The expression level of Ebp1 protein and gene in bladder cancer tissues was significantly lower than that in adjacent normal bladder tissues (P < 0.01). When categorized into low vs. high expression, the down-regulation of Ebp1 protein was associated with the advanced pathologic stage (P = 0.036) and the high histologic grade (P = 0.001) of patients with bladder cancer. Moreover, following the transfection of Ebp1 in bladder cancer cells, not only cell proliferation and cell invasion decreased significantly, but also the cell cycle was blocked at G0/G1 stage. Our data suggest for the first time that the down-regulation of Ebp1 closely correlates with advanced clinicopathological characteristics of human bladder cancer. Furthermore, Ebp1 plays an important role in the bladder cancer cells' proliferation by regulating the cancer cell cycle from G0/G1 to S.

SOXs in human prostate cancer: implication as progression and prognosis factors.

BACKGROUND: SOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa). METHODS: The gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa. RESULTS: The microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance. CONCLUSIONS: Our data offer the convince evidence that the dis-regulation of SOX7, SOX9 and SOX10 may be associated with the aggressive progression of PCa. SOX7 and SOX9 may be potential markers for prognosis in PCa patients. Interestingly, the down-regulation of SOX7 and the up-regulation of SOX9 may be important mechanisms for castration-resistant progression of PCa.

Analysis of genetic aberrations on chromosomal region 8q21-24 identifies E2F5 as an oncogene with copy number gain in prostate cancer.

The copy number gain of genes in chromosomal region 8q21-24 has been demonstrated to be associated with genesis and progression of prostate cancer (PCa). The aim of this study was to identify novel and effective molecular markers in this chromosomal region for PCa. The differentially expressed genes in PCa specimens were screened by gene microarray analysis, which was validated by RT-QPCR analysis. Then, the DNA qPCR analysis was carried out to detect the copy number changes of these differentially expressed genes. Moreover, the clinical significance of candidate markers (MYC and E2F5) in PCa were further determined. E2F5 and MYC were identified as candidate markers in PCa tissues and PCa cell lines. The DNA qPCR revealed the significant copy number gains of E2F5 and MYC in PCa tissues but not in PCa cell lines. In addition, Western blot analysis and immunohistochemical staining both found the significant higher expression of E2F5 and MYC proteins in PCa tissues than those in adjacent benign specimens (all P < 0.01). Moreover, the overexpression of E2F5 protein was significantly associated with a high Gleason score (P < 0.01), an advanced clinical stage (P = 0.01), a positive metastasis (P < 0.01) and PSA Failure (P < 0.01). The overexpression of MYC was more frequently found in PCa tissues with positive metastasis (P = 0.02) and PSA failure (P = 0.02). Interestingly, there was a close correlation in the expression level of MYC in PCa tissues with that of E2F5 (r ( s ) = 0.5, P ≤ 0.001). Our data offers the convincing evidence that the copy number gains of E2F5 and MYC may play an important role in genesis and progression of PCa. Especially, E2F5 may be a novel potential candidate marker for malignant PCa.

MicroRNA-23b downregulates peroxiredoxin III in human prostate cancer.

To investigate the mechanism by which peroxiredoxin III (PRDX3) is altered in human prostate cancer (PCa), we used microRNA (miRNA) target prediction program and miRNA microarray to predict and identify miR-23b as a candidate miRNA that targets PRDX3. We showed that miR-23b suppresses PRDX3 protein expression in human DU145 cells under normal and hypoxic conditions. Additionally, the clinical significance of miR-23b and PRDX3 expression in PCa patients was also confirmed. In conclusion, our data suggest that the effects of PRDX3 in PCa progression may be caused by the regulation function of miR-23b, and consequently, miR-23b may be involved in the response of PCa cells to hypoxia stress.