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Hepatology. 2017 Oct;66(4):1151-1164. doi: 10.1002/hep.29270. Epub 2017 Aug 26.

Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression.

Han D1,2, Li J1, Wang H3, Su X2, Hou J2, Gu Y2, Qian C2, Lin Y2, Liu X2, Huang M2, Li N2, Zhou W4, Yu Y2, Cao X1,2,3.

Author information

1
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
2
National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
3
Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
4
Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.

Abstract

Noncoding RNAs play important roles in cancer biology, providing potential targets for cancer intervention. As a new class of endogenous noncoding RNAs, circular RNAs (circRNAs) have been recently identified in cell development and function, and certain types of pathological responses, generally acting as a 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 (mitochondrial translation optimization 1 homologue; hsa_circRNA_0007874/hsa_circRNA_104135) as one circRNA significantly down-regulated in HCC tissues. HCC patients with low circMTO1 expression had shortened survival. By using a biotin-labeled circMTO1 probe to perform RNA in vivo precipitation in HCC cells, we identified miR-9 as the circMTO1-associated miRNA. Furthermore, silencing of circMTO1 in HCC could down-regulate 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 small interfering RNA promoted tumor growth in HCC-bearing mice 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. (Hepatology 2017;66:1151-1164).

PMID:
28520103
DOI:
10.1002/hep.29270
[Indexed for MEDLINE]

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