Expression profile of oncomiRs and tumor-suppressor miRs in urothelial carcinoma of the bladder.

<p>Introduction & Objectives: Micro-RNAs are small, regulatory molecules approximately 21-24 nucleotides in length. They function at the post-transcriptional level by controlling the expression of more than 50% of human protein-coding genes and play an essential role in cell signaling pathways. Our goal was explore the expression profile of oncomiRs and tumor-suppressor miRs, and to define their possible correlations in urothelial carcinoma of the bladder (BC).</p> <p>Materials & Methods: Seventy-seven primary BCs, along with 77 matched tumor-associated normal samples were investigated for the expression of 12 micro-RNAs using qPCR. Relationships between the expression of miR-10b, miR19a, miR19b, miR-21, miR-122a, miR-145_1, miR-205_1, miR-210, miR-221, miR-222, miR-378-1 and miR-296-5p and the pathologic features of the tumors were also examined.</p> <p>Results: The majority of the micro-RNAs exhibited down-regulation in BC vs. normal tissue [miR-10b (p=0.0007), miR-19a (p=0.012), miR-19b (p=0.0361), miR-126_1 (p=0.0021), miR-145_1 (p<0.0001), miR-221 (p<0.0001), miR-296-5p (p<0.0001), miR-378-1 (p<0.0001)]. miR-21, miR-205_1 and miR-210 expression levels did not present difference between BC and normal tissue. However, we noticed a great range in the x-fold expression values of all micro-RNAs. The median x-fold expression (range) was as follows: miR-10b, 0.45 (0-12.58); miR-19a, 0.56 (0-25.63); miR-19b, 0.50 (0-18.90); miR-21, 0.96 (0-52.95); miR-126_1, 0.36 (0-42.62); miR-145_1, 0.04 (0-56.36); miR-205_1, 1.07 (0.01-36.42); miR-210, 1.09 (0-44.43); miR-221, 0.32 (0-33.51); miR-296-5p, 0.08 (0-75.24); miR-378-1, 0.17 (0-3.66). Significant correlations among all of the studied microRNAs were scored both in BC and control tissue.</p> <p>Conclusions: Different micro-RNAs are deregulated in BC through down-regulation. A synergistic involvement of these genes in the development of BC is implied.</p

MiR-21 can be used as independent prognostic factor for survival and metastasis in urinary bladder cancer.

<p>Introduction & Objectives: Our goal was to correlate the expression of 12 micro-RNAs with the corresponding expression of FGF2, OPN and VEGFA. Gene expression was correlated with the overall and cancer-specific survival of patients suffering from urinary bladder cancer (BC), as well as with recurrence and metastasis.</p> <p>Materials & Methods: Gene expression were acquired by qPCR, from 77 BC specimens. Correlation of the gene expression with survival, recurrence and metastasis was employed by SPSS.</p> <p>Results: High expression of miR-21 correlated with worse overall survival (p=0.0099). Univariate analysis showed that miR-21 and miR-210 can be used as independent prognostic factors for overall survival (p=0.015 and p=0.049, respectively). Moreover, univariate analysis revealed that miR-21 can be used as independent prognostic factor for metastasis (p=0.049). Multivariate analysis revealed that miR-21, miR-210 and miR-378_1 can be used as independent prognostic factors for overall survival (p=0.005, p=0.033 and p=0.012, respectively); miR-21 and miR-378_1 can be used as independent prognostic factors for recurrence (p=0.030 and p=0.031, respectively); and miR-21 can be used as independent prognostic factors for metastasis (p=0.049). FGF2 was positively correlated with the majority of the miRs both in BC and normal tissue (p<0.001). OPN was positively correlated with miR-145_1 (p=0.015) in BC, and with miR-296-5p (p=0.017) in normal tissue. VEGFA was positively correlated with miR-21 in BC (p=0.043), and with miR-205_1 (p=0.045), FGF2 (p=0.004) and OPN (p<0.001) in normal tissue.</p> <p>Conclusions: miR-21 can be used as independent prognostic factor both for overall patient survival and metastasis of BC. miR-210 is an independent prognostic factor for overall survival.</p

microRNA implication in urinary bladder cancer.

<p>INTRODUCTION: microRNAs (miRNAs) are a class of ~22 nt non-coding RNAs that regulate gene expression post-transcriptionally. The oncogenic miRNAs (oncomiRs) display anti-apoptotic activity and are over-expressed in cancer cells, whereas, miRNAs with anti-proliferative and pro-apoptotic activity function as tumor-suppressor genes and are under-expressed in cancer cells.</p> <p>AIM OF STUDY: Our goal was to investigate the expression profile of a various oncomiRs and tumor-suppressor miRs in urinary bladder cancer (BC).</p> <p>MATERIALS AND METHODS: Seventy-seven urinary BC cases, along with 77 matched tumor-associated normal samples were investigated for the expression of 11 miRNAs using qPCR. The relationship among the expression of miR-10b, miR-19a, miR-19b, miR-21, miR-126, miR-145, miR-205, miR-210, miR-221, miR-296-5p and miR-378-1, as well as with the pathologic features of the tumors, was further examined. The influence of miR expression on the overall and cancer-specific survival of the patients, as well as putative target genes of the up- and down-regulated miRNAs were also predicted. RESULTS: As expected, the majority of the microRNAs studied (miR-10b, miR-19a, miR-19b, miR-126_1, miR-145, miR-221, miR-296-5p and miR-378-1) exhibited significant down-regulation in BC vs. the normal tissue. A great range in the x-fold expression values of all microRNAs was noticed. High expression of miR-21 correlated with worse overall survival (p=0.0099). Univariate analysis showed that miR-21 and miR-210 can be used as independent prognostic factors for overall survival (p=0.015 and p=0.049, respectively). Moreover, univariate analysis revealed that miR-21 can be used as independent prognostic factor for metastasis (p=0.049). Multivariate analysis revealed that miR-21, miR-210 and miR-378 can be used as independent prognostic factors for overall survival (p=0.005, p=0.033 and p=0.012, respectively); miR-21 and miR-378 can be used as independent prognostic factors for recurrence (p=0.030 and p=0.031, respectively); and miR-21 can be used as independent prognostic factors for metastasis (p=0.049).</p> <p>DISCUSSION: The data reported here demonstrate that several microRNAs are deregulated in BC through down-regulation. miR-21 can be used as independent prognostic factor both for patient survival and metastasis. miR-210 can be used as an independent prognostic factor for overall survival.</p