Supplementary Figure 3 from Genomic Profiling of MicroRNAs in Bladder Cancer: miR-129 Is Associated with Poor Outcome and Promotes Cell Death In vitro</i> (original) (raw)
Related papers
Cancer Research, 2009
microRNAs (miRNA) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Here, we profiled the expression of 290 unique human miRNAs in 11 normal and 106 bladder tumor samples using spotted locked nucleic acid-based oligonucleotide microarrays. We identified several differentially expressed miRNAs between normal urothelium and cancer and between the different disease stages. miR-145 was found to be the most down-regulated in cancer compared with normal, and miR-21 was the most upregulated in cancer. Furthermore, we identified miRNAs that significantly correlated to the presence of concomitant carcinoma in situ. We identified several miRNAs with prognostic potential for predicting disease progression (e.g., miR-129, miR-133b, and miR-518c*). We localized the expression of miR-145, miR-21, and miR-129 to urothelium by in situ hybridization. We then focused on miR-129 that exerted significant growth inhibition and induced cell death upon transfection with a miR-129 precursor in bladder carcinoma cell lines T24 and SW780 cells. Microarray analysis of T24 cells after transfection showed significant miR-129 target downregulation (P = 0.0002) and pathway analysis indicated that targets were involved in cell death processes. By analyzing gene expression data from clinical tumor samples, we identified significant expression changes of target mRNA molecules related to the miRNA expression. Using luciferase assays, we documented a direct link between miR-129 and the two putative targets GALNT1 and SOX4. The findings reported here indicate that several miRNAs are differentially regulated in bladder cancer and may form a basis for clinical development of new biomarkers for bladder cancer. [Cancer Res 2009;69(11):4851-60]
Urology journal, 2015
To evaluate the expression of microRNAs in tissue samples from patients with bladder cancer and to compare it with healthy adjacent tissue samples as controls. Thirty five tissue samples from patients with newly diagnosed untreated bladder transitional cell carcinoma and 35 adjacent normal urothelium were collected during 2013 to 2014. TRIzol reagent was used to isolate total RNA including microRNAs. RNA concentration and purity were determined using a nanodrop spectrophotometer. Also 1% agarose gel electrophoresis was used to assess integrity of RNA. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) method was performed using the PARSGENOME microRNA RT-PCR system. Data was analyzed by STATA 11. A couple of patients were female the remainder were male. Mean age of patients were 71.06 ± 11.43 years. The expression level of miR-30b, miR-141 and miR-200c in case group were significantly higher than that of control normal tissue samples. miR-141 had higher expression rat...
Molecular Biology Reports, 2020
Background Given the high recurrence and progression rates and the absence of reliable markers for early detection and prognosis prediction of patients with urothelial bladder cancer (BCa), the exploration of new biomarkers with high specificity is imperative. Mainly, microRNAs (miRNAs), which are involved in the initiation and the progression of BCa. Herein, the expression patterns of miR-182, miR-205, miR-27a and miR-369 were evaluated in patients with urothelial BCa. Methods and results The expression levels of the miRNAs were investigated in 90 FFPE tissue samples (23 LG NMIBC, 44 HG NMIBC, 23 MIBC) and 10 non tumoral bladder tissues using TaqMan based RT-qPCR. Data analysis was performed using 2 −ΔΔCT method. Correlation to clinical characteristics of the patients was performed using descriptive statistics and the receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value of all miRNAs. MiR-27a, miR-205 and miR-369 were down-regulated whereas miR-182 was up-regulated in patients compared to controls (p < 0.001). MiR-205 and miR-182 positively segregate between NMIBC and MIBC (p = 0.002 and p = 0.000 respectively) whereas the distribution of miR-27a's expression among these tumor groups was almost significant (p = 0.05) and that of miR-369's expression was irrelevant (p = 0.618). Interestingly, miR-182 was discriminative between LG NMIBC and HG NMIBC (p < 0.001) and Ta/T1 tumors (p = 0.000). Furthermore, high levels of miR-182 were potentially predictive of progression in NMIBC patients (p = 0.01). Conclusion Collectively, a selection of miRNAs was found to be aberrantly expressed in BCa suggesting a potential diagnostic value in BCa. In addition, the clinical value of miR-182 and miR-205 as potential prognosis biomarkers was highlighted. Indeed, our data provide additional insights into cancer biology. Further functional or target studies are mandatory to strengthen these findings.
Carcinogenesis, 2015
Accurate prognosis is a key-factor in establishing optimal therapeutic decisions; yet in the case of bladder cancer (BlCa) current prognostic indicators cannot ensure optimal disease management. Here we aimed to evaluate the previously unexplored clinical potential of the urological cancer-related miR-145, miR-143 and miR-224 in BlCa. A total of 279 bladder tissue specimens were included in this study (133 BlCa, 107 adjacent normal and 39 healthy samples). Total RNA was extracted from tissues, it was polyadenylated and reverse transcribed to cDNA. The expression of target molecules was measured via qPCR. The expression levels of both miR-143 and miR-145 were significantly decreased, whereas those of miR-224 were increased in BlCa. ROC curve analysis indicated a significant discriminatory capacity for miR-143/miR-145 levels. Important associations with disease aggressiveness were observed for all three miRNAs; elevated levels were observed in tumors of higher stage and grade, as well...
Identification of novel microRNA targets based on microRNA signatures in bladder cancer
International Journal of Cancer, 2009
MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate protein-coding genes. To identify miRNAs that have a tumor suppressive function in bladder cancer (BC), 156 miRNAs were screened in 14 BCs, 5 normal bladder epithelium (NBE) samples and 3 BC cell lines. We identified a subset of 7 miRNAs (miR-145, miR-30a-3p, miR-133a, miR-133b, miR-195, miR-125b and miR-199a*) that were significantly downregulated in BCs. To confirm these results, 104 BCs and 31 NBEs were subjected to real-time RT-PCR-based experiments, and the expression levels of each miRNA were significantly downregulated in BCs (p < 0.0001 in all). Receiver-operating characteristic curve analysis revealed that the expression levels of these miRNAs had good sensitivity (>70%) and specificity (>75%) to distinguish BC from NBE. Our target search algorithm and gene-expression profiling in BCs (Kawakami et al., Oncol Rep 2006;16:521-31) revealed that Kera-tin7 (KRT7) mRNA was a common target of the downregulated miRNAs, and the mRNA expression levels of KRT7 were significantly higher in BCs than in NBEs (p 5 0.0004). Spearman rank correlation analysis revealed significant inverse correlations between KRT7 mRNA expression and each downregulated miRNA (p < 0.0001 in all). Gain-of-function analysis revealed that KRT7 mRNA was significantly reduced by transfection of 3 miRNAs (miR-30-3p, miR-133a and miR-199a*) in the BC cell line (KK47). In addition, significant decreases in cell growth were observed after transfection of 3 miRNAs and si-KRT7 in KK47, suggesting that miR-30-3p, miR-133a and miR-199a* may have a tumor suppressive function through the mechanism underlying transcriptional repression of KRT7. ' 2009 UICC
International journal of molecular and cellular medicine, 2015
Bladder cancer (BC) ranks the second most common genitourinary tract malignant tumor with high mortality and 70% recurrence rate worldwide. MiRNAs expression has noticeable role in bladder tumorigenesis. The purpose of this study was to assess miR-200c, miR-30b and miR-141 in tissue samples of patients with BC and healthy adjacent tissue samples and their association with muscle invasion, grade and the size of the tumor. Transurethral resection tissue samples were collected from thirty- five newly diagnosed untreated patients with BC from 2013 to 2014. The control group consisted of adjacent normal urothelium. All samples, observed by two pathologists, were diagnosed transitional cell carcinomas (TCC) with the proportion of tumor cells greater than 80%. Total RNA including miRNAs was extracted from about 50 mg tissue samples by applying TRIzol reagent. 2((-ΔΔ CT)) method was used to calculate relative quantification of miRNA expression. Two of 35 patients were females and the other 3...
Up-regulation of microRNA in bladder tumor tissue is not common
International Urology and Nephrology, 2009
MicroRNAs (miRNAs) have recently been shown to down-regulate gene expression by targeting mRNA translation and to play a critical role in tumorigenesis; how they regulate bladder tumor development, particularly in patients, is, however, poorly understood. The difference in miRNA expression in a bladder tumor compared with healthy tissue from the same patients was examined using microR-NA arrays in seven patients. Here, we showed that up-regulation of miRNA was not commonly found in this limited number of patients, and four miRNAs (miR-26a, miR-29c, miR-30c, miR-30e-5p) were down-regulated as a common marker in patients with a 1-3 grade of disease. Our data suggest that instead of up-regulation of carcinogenic miRNAs, loss of regulation of these miRNA may be critical for bladder tumor development in patients.
An evaluation of urinary microRNA reveals a high sensitivity for bladder cancer
British journal of cancer, 2012
Urinary biomarkers are needed to improve the care and reduce the cost of managing bladder cancer. Current biomarkers struggle to identify both high and low-grade cancers due to differing molecular pathways. Changes in microRNA (miR) expression are seen in urothelial carcinogenesis in a phenotype-specific manner. We hypothesised that urinary miRs reflecting low- and high-grade pathways could detect bladder cancers and overcome differences in genetic events seen within the disease. We investigated urinary samples (n=121) from patients with bladder cancer (n=68) and age-matched controls (n=53). Fifteen miRs were quantified using real-time PCR. We found that miR is stable within urinary cells despite adverse handling and detected differential expression of 10 miRs from patients with cancer and controls (miRs-15a/15b/24-1/27b/100/135b/203/212/328/1224, ANOVA P<0.05). Individually, miR-1224-3p had the best individual performance with specificity, positive and negative predictive values...