Circular RNA circ_0003028 regulates cell development through modulating miR-498/ornithine decarboxylase 1 axis in hepatocellular carcinoma.

Abstract

Circular RNA has been revealed to participate in multiple biological functions and contribute to various diseases' progression. This study aims to clarify the role of circ_0003028 and its potential molecular mechanism in hepatocellular carcinoma (HCC). The levels of circ_0003028, miR-498, and ornithine decarboxylase 1 (ODC1) mRNA were examined by quantitative real-time PCR. The cell proliferation ability was detected via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, colony formation, and 5-ethynyl-2'-deoxyuridine assays. The apoptotic rate was evaluated through flow cytometry. The migration and invasion capacity was tested by using wound healing assay and transwell assay. The protein levels of E-cadherin, N-cadherin, and vimentin were measured by western blot assay. The ceRNA regulatory mechanism of circ_0003028 was observed via dual-luciferase reporter and RNA pull-down assays. The mice xenograft models were constructed to confirm the oncogenicity of circ_0003028 in HCC in vivo . Circ_0003028 and ODC1 were upregulated, whereas miR-498 was downregulated in HCC tissues and cells. Circ_0003028 knockdown inhibited cell proliferation and metastasis, and promoted apoptosis. MiR-498 was a direct target of circ_0003028, and inhibition of miR-498 reversed the inhibitory effect of circ_0003028 silencing on HCC progression. Moreover, ODC1 was a direct target of miR-498 and ODC1 overexpression abated the anticancer roles of miR-498 in HCC. Additionally, circ_0003028 regulated ODC1 expression by sponging miR-498. Finally, we found that circ_0003028 could induce epithelial-mesenchymal transition of HCC cells by exosome pathway. In brief, the results demonstrated that circ_0003028 exerted tumourigenicity roles via miR-498/ODC1 signaling axis, providing a promising biomarker and therapeutic target for HCC.