Circular RNA circMTO1 Acts as the Sponge of MicroRNA-9 to Suppress Hepatocellular Carcinoma Progression
Circular RNA circMTO1 Acts as the Sponge of MicroRNA-9 to Suppress Hepatocellular Carcinoma Progression
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DOI：
10.1002/hep.29270
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发表时间：
2017-10-01
期刊：
影响因子：
13.5
通讯作者：
Cao, Xuetao
中科院分区：
文献类型：
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作者：
Han, Dan;Li, Jiangxue;Cao, Xuetao
非编码RNA在癌症生物学中起着重要作用，为癌症干预提供了潜在的靶点。作为一类新的内源性非编码RNA，环状RNA（circular RNA，circRNA）在细胞发育、功能和某些病理反应中起着海绵状的微小RNA（microRNA，miRNA）的作用。鉴定失调的circRNA及其在癌症中的作用引起了人们的广泛关注。然而，circRNA在人肝细胞癌（HCC）中的表达谱和功能仍有待研究。在这里，我们分析了人circRNA在HCC组织中的表达谱，并将circMTO 1（线粒体翻译优化1同源物; hsa_circRNA_ 0007874/hsa_circRNA_104135）鉴定为在HCC组织中显著下调的一种circRNA。circMTO 1低表达的HCC患者生存期缩短。通过使用生物素标记的circMTO 1探针在HCC细胞中进行RNA体内沉淀，我们鉴定了miR-9为circMTO 1相关的miRNA。此外，肝癌中circMTO 1的沉默可下调致癌miR-9的靶点p21，从而促进肝癌细胞的增殖和侵袭。此外，circMTO 1沉默的促肿瘤作用被miR 9抑制剂阻断。胆固醇结合的circMTO 1小干扰RNA的瘤内给药促进肝癌荷瘤小鼠体内肿瘤生长。结论：circMTO 1通过充当致癌miR-9的海绵以促进p21表达来抑制HCC进展，这表明circMTO 1是HCC治疗的潜在靶点。肝癌组织中circMTO 1表达的降低可能是患者生存不良的预后指标。
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.