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Resistance to cisplatin-based chemotherapy is a major cause of treatment failure in advanced bladder cancer (BC) patients. There is increasing evidence that microRNAs are involved in the development and progression of BC. However, little is known about the function of microRNAs in predicting the effect of adjuvant chemotherapy on BC survival and regulating response to cisplatin. To address this issue, we employed RT-qPCR to evaluate the clinical significance of miR-203 expression in 108 tissues of BC patients receiving cisplatin-based adjuvant chemotherapy, and performed in vitro studies to explore chemotherapeutic sensitivity to cisplatin in miR-203 overexpressing BC cells. We found miR-203 levels were significantly lower in BC progression group than non-progression group (P<0.001). ROC curve analysis illustrated miR-203 could significantly distinguish progressed patients from those without progression (P<0.001), yielding an area under the ROC curve of 0.839 (95% CI, 0.756–0.903). Moreover, low miR-203 expression correlated with shortened progression free survival (PFS) and overall survival (OS) of BC patients, and was an independent prognostic factor. Overexpression of miR-203 in 5637 and T24 BC cells could decrease cell viability, enhance cisplatin cytotoxicity, and promote apoptosis. Western blotting and luciferase reporter assay showed Bcl-w and Survivin were direct downstream targets of miR-203. There was also a significant inverse association between miR-203 and Bcl-w or Survivin expression in BC tissues (r = -0.781, -0.740, both P<0.001). In conclusion, decreased miR-203 predicts progression and poor prognosis for BC patients treated with cisplatin-based chemotherapy while miR-203 overexpression can enhance cisplatin sensitization by promoting apoptosis via directly targeting Bcl-w and Survivin. [ABSTRACT FROM AUTHOR]

MiR-210 is the master hypoxamir that generally exhibits oncogenic properties in most human solid tumors including bladder cancer (BC). However, it remains unknown about the clinical significance of circulating miR-210 levels in BC. In this study, we found that serum miR-210 was up-regulated in patients with BC, and serum levels of miR-210 increased with advancing stage and grade. Moreover, serum miR-210 expression was found to be significantly reduced in paired post-operative samples and elevated in most patients with relapsed BC. Taken together, our data suggest that serum miR-210 could be a potential noninvasive biomarker for screening, predicting and monitoring BC. [ABSTRACT FROM AUTHOR]

Cellular chemotaxis is the best-known function of chemokine receptors which are closely linked with tumor metastasis. In fact, positive expression of chemokine receptors could also be identified even in some patients without metastatic tumors, while the clinical relevance of this data has not been fully established. Our studies were designed to clarify the CCR4 expression profiles and to explore its potential role in histologically node-negative (pN0) gastric cancer (GC). Immunohistochemistry (IHC) or immunohistofluorescence (IHF) analysis was performed on specimens obtained from 108 patients with pN0 GC. We found that CCR4 was aberrantly over-expressed inpN0 GC tissues, with different expression patterns on tumor cells and being associated with T-stage (P = 0.002). The matrigel in vitro invasion assay revealed that over-expression of CCR4 in GC cell lines significantly enhanced the invasive capacity of these cells. Results from real-time RT-PCR and gelatinzymography showed a significant increase in matrix metalloproteinase (MMP)-9 production induced by the forced expression of CCR4 in GC cell lines. Our data suggest that the aberrant CCR4 expression is involved in tumor invasion of pN0 GC and, conceivably, antagonists of CCR4 might be useful candidates for controlling early events in tumor progression. [ABSTRACT FROM AUTHOR]

MicroRNA-214 (miR-214) has been reported to be dysregulated in human bladder cancer tissues. We aimed to investigate the clinical correlation, biological significance and molecular network of miR-214 in bladder cancer. Our results showed miR-214 was down-regulated in bladder cancer tissues and significantly associated with tumor stage, lymph node status, grade, multifocality, history of non-muscle-invasive bladder cancer (NMIBC). Moreover, miR-214 could serve as an independent factor of recurrence-free survival (RFS) and overall survival (OS) for patients with muscle-invasive bladder cancer (MIBC). Restoration of miR-214 expression in bladder cancer cell lines inhibited cell proliferation, migration, invasion and markedly promoted apoptosis. Dual-luciferase reporter assay recognized PDRG1 as direct downstream target gene of miR-214. PDRG1 was significantly increased in tumors low of miR-214 and knockdown of PDRG1 mimicked the effects of miR-214 overexpression. Our findings manifest that miR-214 could exert tumor-suppressive effects in bladder cancer by directly down-regulating oncogene PDRG1 and suggest an appealing novel indicator for prognostic and therapeutic intervention of bladder cancer. [ABSTRACT FROM AUTHOR]

Zinc finger protein 217 (ZNF217) is essential for cell proliferation and has been implicated in tumorigenesis. However, its expression and exact roles in colorectal cancer (CRC) remain unclear. In this study, we demonstrated that ZNF217 expression was aberrantly upregulated in CRC tissues and associated with poor overall survival of CRC patients. In addition, we found that ZNF217 was a putative target of microRNA (miR)-203 using bioinformatics analysis and confirmed that using luciferase reporter assay. Moreover, in vitro knockdown of ZNF217 or enforced expression of miR-203 attenuated CRC cell proliferation, invasion and migration. Furthermore, combined treatment of ZNF217 siRNA and miR-203 exhibited synergistic inhibitory effects. Taken together, our results provide new evidences that ZNF217 has an oncogenic role in CRC and is regulated by miR-203, and open up the possibility of ZNF217- and miR-203-targeted therapy for CRC. [ABSTRACT FROM AUTHOR]

MicroRNA-210 (miR-210), the master hypoxamir, plays pleiotropic roles in certain cancers; however, its role in the development of human colorectal cancer remains unclear. Herein, we report that miR-210 is frequently up-regulated in colorectal cancer tissues, with high miR-210 expression significantly correlating with large tumor size, lymph node metastasis, advanced clinical stage and poor prognosis. Functionally, miR-210 overexpression promotes the migration and invasion of colorectal cancer cells. Furthermore, miR-210 can be induced by hypoxia and mediates the hypoxia-induced metastasis of colorectal cancer cells. In addition, vacuole membrane protein 1 (VMP1) is identified as the direct and functional target of miR-210. Thus, miR-210 is a useful biomarker for hypoxic tumor cells and a prognostic factor that plays an essential role in colorectal cancer metastasis. [ABSTRACT FROM AUTHOR]

Serum microRNAs (miRNAs) have become a highlighted research hotspot, especially for their great potential as a novel promising non-invasive biomarker in cancer diagnosis. The most frequently used approach for serum miRNAs detection is quantitative real time polymerase chain reaction (qPCR). In order to obtain reliable qPCR data of miRNAs expression, the use of reference genes as endogenous control is undoubtly necessary. However, no systematic evaluation and validation of reference genes for normalizing qPCR analysis of serum miRNAs has been reported in colorectal adenocarcinoma. We firstly profiled pooled serum of colorectal adenocarcinoma, colorectal adenoma and healthy controls and selected a list of 13 miRNAs as candidate reference genes. U6 snRNA (U6) and above-mentioned 13 miRNAs were included in further confirmation by qPCR. As a result, 5 miRNAs (miR-151a-3p, miR-4446-3p, miR-221-3p, miR-93-5p and miR-3184-3p) were not detected in all samples and 2 miRNAs (miR-197-3p and miR-26a-5p) were relatively low with median Cq more than 35, and were excluded from further stability analysis. Then variable stability of other 6 miRNAs (miR-103b, miR-484, miR-16-5p, miR-3615, miR-18a-3p and miR-191-5p) and U6 were evaluated using two algorithms: geNorm and NormFinder which both identified miR-191-5p as the most stably expressed reference gene and selected miR-191-5p and U6 as the most stable pair of reference genes. After validating in an independent large cohorts and selecting miR-92a-3p as target miRNA to evaluate the effect of reference gene, we propose that combination of miR-191-5p and U6 could be used as reference genes for serum microRNAs qPCR data in colorectal adenocarcinoma, colorectal adenoma and healthy controls. [ABSTRACT FROM AUTHOR]