Abstract
Circular RNAs (circRNAs) play essential roles in tumorigenesis and tumor progression. CircRNA GFRA1 (circGFRA1) was dysregulated in many cancer samples and acted as an independent marker for prediction of survivals in various cancer patients. However, the functions and molecular mechanisms of circGFRA1 in hepatocellular carcinoma (HCC) remain unclear. We collected 62 HCC tissues and normal adjacent tissues to evaluate the expression of circGFRA1 and the relationship between circGFRA1 expression and HCC patients’ survival. We carried out a list of characterization experiments to investigate the roles and underling mechanisms of circGFRA1 and miR-498 in HCC progressions. CircGFRA1 was greatly increased in HCC tissues and cells, and the over-expression of circGFRA1 was intimately related with the advanced clinical stage and poor survival of HCC patients. The expression of circGFRA1 was negatively correlated with the expression of miR-498, but a positive correlation was found between circGFRA1 and NAP1L3 expression in HCC tissues. Silencing circGFRA1 inhibited the growth and invasion of hepatocellular carcinoma. Moreover, miR-498 over-expression or NAP1L3 inhibition could abrogate the oncogene role of circGFRA1 in HCC in vivo. Our findings indicated that circGFRA1 contributed to HCC progression by modulating the miR-498/NAP1L3 axis in HCC.
Highlights
Circular RNAs play essential roles in tumorigenesis and tumor progression
CircGFRA1 was markedly over‐expressed in hepatocellular carcinoma (HCC)
The results revealed the oncogenic role of circGFRA1 in HCC
Summary
Circular RNAs (circRNAs) play essential roles in tumorigenesis and tumor progression. Circular RNAs (circRNAs) are newly discovered groups of endogenous non-coding RNAs that could regulate gene expression in m ammals[8,9]. They have been identified to participate in cellular developmental p rocesse[10,11]. Xiong et al reported that circRNAs might act as a new type of potential biomarkers and therapeutic targets for hepatocellular carcinoma[12]. He et al reported that circRNA GFRA1 could regulate neuronal cell survival and differentiation. Considering the significant role of miR-498 in so many cancer types, we are encouraged to discover the role of miR-498 in HCC, as well as its potential interactions with circGFRA1
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