Abstract
Circular RNAs (circRNAs), a kind of non-coding RNAs, have shown large capabilities in gene regulation. However, the mechanisms underlying circRNAs remain largely unknown so far. Recent studies demonstrated that circRNAs play miRNA sponge effects and regulate gene expression by microRNA response elements. Here, we screened circRNA expression profiles of bladder carcinoma using microarray assay. A total of 469 dysregulated circular transcripts are found in bladder cancer compared with normal tissues, among which 285 were up-regulated and 184 were down-regulated. Six circRNAs were identified to have significant differences by qRT-PCR. We speculated that circRNAs might involve in cancer-related pathways via interactions with miRNA by multiple bioinformatical approaches. Therefore, we further predicted that circTCF25 could sequester miR-103a-3p/miR-107, which potentially lead to the up-regulation of thirteen targets related to cell proliferation, migration and invasion. Subsequently, we demonstrated that over-expression of circTCF25 could down-regulate miR-103a-3p and miR-107, increase CDK6 expression, and promote proliferation and migration in vitro and vivo. This is the first study to exploit circRNA profiling and circRNA/miRNA interactions in bladder cancer. Our work laid the foundation to investigate the functions of circRNAs in cancers. The data also suggest that circTCF25 might be a new promising marker for bladder cancer.
Highlights
Bladder cancer is the prevalent malignant tumor at the urinary system
The competitive endogenous RNAs include pseudogene transcripts, long noncoding RNAs, cirular RNAs and mRNAs, and these transcripts can compete for the pool of same microRNA response elements (MREs) to influence the activities of microRNAs in regulating gene expressions[5]
We first reported on circRNA profiles in bladder cancer
Summary
Bladder cancer is the prevalent malignant tumor at the urinary system. The prevalence of 5-year is estimated at 1,110,265 worldwide, ranking the 9th in cancer incidence around the world and the 13th main causes of death by cancer[1,2]. DIANA-miRPath enrichment analysis was performed to identify molecular pathways potentially altered by the expression of those miRNAs. we depicted a network containing thirteen pivotal genes correlated with circTCF25-miR-103a-3p/miR-107 axes. The data suggested that the expression of circRNAs in bladder cancer tissues is different from that in matched non-tumor tissues. The data indicated that microarray analysis was well consistent with qPCR results regarding the expression levels of the six circRNAs (Fig. 4C).
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