Abstract
BackgroundCircular RNA (circRNA) represents a broad and diverse endogenous RNAs that can regulate gene expression in cancer. However, the regulation and function of bladder cancer (BC) circRNAs remain largely unknown.MethodsHere we generated circRNA microarray data from three BC tissues and paired non-cancerous matched tissues, and detected circular RNA-cTFRC up-regulated and correlated with tumor grade and poor survival rate of BC patients. We subsequently performed functional analyses in cell lines and an animal model to support clinical findings. Mechanistically, we demonstrated that cTFRC could directly bind to miR-107 and relieve suppression for target TFRC expression.ResultsWe detected circular RNA-cTFRC up-regulated and correlated with tumor grade and poor survival rate of BC patients. Knock down of cTFRC inhibited invasion and proliferation of BC cell lines in vitro and tumor growth in vivo. Furthermore, the expression of cTFRC correlated with TFRC and negatively correlated with miR-107 both in BC cell lines and BC clinical samples. In addition, up-regulation of cTFRC promoted TFRC expression and contributed to an epithelial to mesenchymal transition phenotype in BC cells. Finally, we found that cTFRC acts as a competing endogenous RNA (ceRNA) for miR-107 to regulate TFRC expression.ConclusionscTFRC may exert regulatory functions in BC and may be a potential marker of BC diagnosis or progression.
Highlights
Circular RNA represents a broad and diverse endogenous RNAs that can regulate gene expression in cancer
Results cTFRC expression is significantly correlated with poor prognosis of bladder cancer (BC) patients To investigate the Circular RNA (circRNA) expression profile in BC tissues, we first analyzed three pairs of BC tissue samples (3 BC tissues and three matched non-tumor bladder tissues) by using the circRNA microarray
Through expression intensity sorting within BC tumor and non-tumor groups, we found that cTFRC expression was consistently and significantly increased in BC tumor tissues as compared to the matching controls (Fig. 1a)
Summary
Circular RNA (circRNA) represents a broad and diverse endogenous RNAs that can regulate gene expression in cancer. The regulation and function of bladder cancer (BC) circRNAs remain largely unknown. According to the Global Cancer Statistics, about 79,030 new cases of bladder cancer are diagnosed annually in the United States, and an estimated 16,870 patients will die of this disease [2]. The existence of circRNAs was first observed in eukaryotic cells nearly 40 years ago by using an electron microscope [4]. CircRNAs have been verified to be associated with several diseases such as brain dis-function or neurodegenerative diseases like Alzheimer’s disease and several cancers. Unlike linear RNAs, circRNAs have the prominent feature of non-canonical splicing with no free 3′ and 5′ end, which enables them to be resistant to RNA
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