Circular RNA MTO1 acts as the sponge of miR-9 to suppress hepatocellular carcinoma progression

Abstract

Non-coding RNAs play important roles in cancer biology, providing potential targets for cancer intervention. As a new class of endogenous non-coding RNAs, circular RNAs (circRNAs) have been recently identified in the development, cell function and certain types of pathological responses, generally acting as microRNA (miRNA) sponge to regulate gene expression. Identifying the deregulated circRNAs and their roles in cancer has attracted much attention. However, the expression profile and function of circRNAs in human hepatocellular carcinoma (HCC) remain to be investigated. Here, we analyzed the expression profile of human circRNAs in HCC tissues and identified circMTO1 (hsa_circRNA_0007874/hsa_circRNA_104135) as one circRNA significantly downregulated in HCC tissues. HCC patients with low circMTO1 expression had shortened survival. By using biotin-labeled circMTO1 probe to perform RNA in vivo precipitation (RIP) in HCC cells, we identified miR-9 as the circMTO1-associated microRNA. Furthermore, silencing of circMTO1 in HCC could downregulate p21, the target of oncogenic miR-9, resulting in the promotion of HCC cell proliferation and invasion. In addition, the tumor-promoting effect of circMTO1 silencing was blocked by miR9 inhibitor. Intratumoral administration of cholesterol-conjugated circMTO1 siRNA promoted HCC tumor growth in vivo. Conclusion: circMTO1 suppresses HCC progression by acting as the sponge of oncogenic miR-9 to promote p21 expression, suggesting that circMTO1 is a potential target in HCC treatment. The decrease of circMTO1 in HCC tissues may serve as a prognosis predictor for poor survival of patients. This article is protected by copyright. All rights reserved.

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