MicroRNA Expression Signatures of Bladder Cancer Revealed by Deep Sequencing

Abstract

BackgroundMicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression. They are aberrantly expressed in many types of cancers. In this study, we determined the genome-wide miRNA profiles in bladder urothelial carcinoma by deep sequencing.Methodology/Principal FindingsWe detected 656 differentially expressed known human miRNAs and miRNA antisense sequences (miRNA*s) in nine bladder urothelial carcinoma patients by deep sequencing. Many miRNAs and miRNA*s were significantly upregulated or downregulated in bladder urothelial carcinoma compared to matched histologically normal urothelium. hsa-miR-96 was the most significantly upregulated miRNA and hsa-miR-490-5p was the most significantly downregulated one. Upregulated miRNAs were more common than downregulated ones. The hsa-miR-183, hsa-miR-200b∼429, hsa-miR-200c∼141 and hsa-miR-17∼92 clusters were significantly upregulated. The hsa-miR-143∼145 cluster was significantly downregulated. hsa-miR-182, hsa-miR-183, hsa-miR-200a, hsa-miR-143 and hsa-miR-195 were evaluated by Real-Time qPCR in a total of fifty-one bladder urothelial carcinoma patients. They were aberrantly expressed in bladder urothelial carcinoma compared to matched histologically normal urothelium (p<0.001 for each miRNA).Conclusions/SignificanceTo date, this is the first study to determine genome-wide miRNA expression patterns in human bladder urothelial carcinoma by deep sequencing. We found that a collection of miRNAs were aberrantly expressed in bladder urothelial carcinoma compared to matched histologically normal urothelium, suggesting that they might play roles as oncogenes or tumor suppressors in the development and/or progression of this cancer. Our data provide novel insights into cancer biology.

microRNA-195 inhibits cell proliferation in bladder cancer via inhibition of cell division control protein 42 homolog/signal transducer and activator of transcription-3 signaling

“…In the present study, it was found that miR-195 expression was significantly downregulated in bladder cancer tissues compared with that in their matched normal adjacent tissues, which was consistent with other studies (4,17). The first finding that miR-195 expression was notably downregulated in bladder cancer tissues when compared with that in normal bladder epithelium tissues was reported in a study by Ichimi et al (4).…”

“…The first finding that miR-195 expression was notably downregulated in bladder cancer tissues when compared with that in normal bladder epithelium tissues was reported in a study by Ichimi et al (4). Han et al (17) then examined the expression profile of miRNAs using deep sequencing and qPCR, and showed that miR-195 expression was notably downregulated in bladder cancer tissues compared with that in matched histologically normal urothelium. More recently, Itesako et al (18) examined the miRNA expression signature of bladder cancer by deep sequencing, and revealed the functional significance of the miR-195/497 cluster.…”

miR-125a-5p upregulation suppresses the proliferation and induces the cell apoptosis of lung adenocarcinoma by targeting NEDD9

“…These miRNAs regulate gene expression by targeting the 3' untranslated regions (3'UTRs) of mRNAs (1)(2)(3)(4)(5)(6). Numerous studies have shown that miRNAs act as intrinsic regulators of many cellular processes, including cell proliferation, apoptosis, invasion and differentiation (7)(8)(9)(10)(11)(12). Aberrant expression of miRNAs has been found to be associated with the development and progression of numerous types of cancers.…”

A new microRNA target prediction tool identifies a novel interaction of a putative miRNA with CCND2

“…37 Importantly, supporting evidence from recent deep sequencing studies do not report an expression for c-miRCh9 among the identified microRNA expression signatures of bladder cancer. 40 Computational identification of a highly significant and evolutionary conserved target binding site for this potential miRNA in the CCND2 oncogene using Targetprofiler was the initial incentive for performing reporter gene assays. CCND2 is a well known cyclin which functions in the cell mut-3'UTR).…”