Abstract
Increasing circular RNAs (circRNAs) have been reported to act as key players in human malignancies. However, the expression, role, and mechanism of circRNAs in HCC are not well elucidated. In this study, some differentially expressed circRNAs (DECs) between hepatocellular carcinoma (HCC) and normal tissues were identified using three circRNA microarrays (Gene Expression Omnibus [GEO]: GSE78520, GSE94508, and GSE97332). Twenty-one DECs were found to be commonly upregulated in all the three datasets. Among the 21 DECs, hsa_circ_0001955 ranked as the top three most upregulated DECs in GEO: GSE78520, GSE94508, and GSE97332. Moreover, hsa_circ_0001955 expression in HCC cells and tissues was significantly higher than that in corresponding normal controls. Functional experiments revealed that knockdown of hsa_circ_0001955 markedly inhibited proliferation, migration, and invasion of HCC, and its overexpression led to the opposite effects. hsa_circ_0001955 was mainly located in the cytoplasm, in which hsa_circ_0001955 could directly bind to miR-145-5p. miR-145-5p was downregulated in HCC, and its expression was negatively linked to hsa_circ_0001955 expression. Furthermore, we identified that NRAS was a downstream direct target of the hsa_circ_0001955/miR-145-5p axis in HCC. Collectively, our findings demonstrate the oncogenic roles of the hsa_circ_0001955/miR-145-5p/NRAS axis in HCC, which may represent a potential therapeutic target for HCC.
Highlights
Liver cancer is one of the leading causes of cancer-associated mortality all over the world
Liu et al.[13] suggested that circRNA-5692 inhibited hepatocellular carcinoma (HCC) progression by sponging miR-328-5p to promote DAB2IP expression, Wang et al.[14] reported that SOX9-induced circ-FOXP1 enhanced HCC progression via sponging miR-875-3p and miR-421, and Su et al.[15] found that circRNA Cdr1as functioned as a competitive endogenous RNAs (ceRNAs) to promote HCC progression
Effects on HCC In this part, we aimed to study the role of miR145-5p and its effect on hsa_circ_0001955mediated oncogenic functions in HCC
Summary
Liver cancer is one of the leading causes of cancer-associated mortality all over the world. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for approximately 80% of all cases.[1] To date, multiple risk factors have been found to link to HCC occurrence and development, such as virus infection,[2] alcohol abuse,[3] non-alcoholic fatty liver disease,[4] and cirrhosis.[5] several lines of evidence have indicated that accumulation of genetic and epigenetic changes leads to HCC.[6]. The knowledge of circRNA’s function and mechanism in HCC remains insufficient and needs to be further investigated
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