CircRNA_0008194 functions as a ceRNA to promote invasion of hepatocellular carcinoma via inhibiting miR-190a/AHNAK signaling pathway

CircRNA_0008194作为ceRNA通过抑制miR-190a/AHNAK信号通路促进肝细胞癌侵袭

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Abstract

BACKGROUND: Hepatitis B virus infection was identified as the main risk factor of hepatocellular carcinoma (HCC) in China, which induced a high morbidity and mortality. In recent years, circRNAs were reported involving in the oncogenesis and development of multiple malignant tumors. METHOD: Bioinformatical analysis has been employed to predict the relevant circRNA with AHNAK. The loss of function and gain of function have been used by knocking-down circRNA through the shRNA technology while overexpressing through lentivirus infection. Dual-luciferase reporter assay was used to detect circRNA binding to miRNA and target genes. We further used immunoprecipitation technique to detect the binding ability between non-coding RNAs. RESULTS: In this study, according to the previous report, we mainly focused on AHNAK, which has been confirmed as an oncogene involving in the metastasis of HCC. Bioinformatics analysis showed that circ_0008194 could be spliced by AHNAK. In this study, the abnormal upregulated circ_0008194 in tumor tissues was detected. The positive correlation between circ_0008194 and AHNAK was also confirmed. Through knockdown and overexpression of circ_0008194, we conducted in vitro functional studies. We found circ_0008194 could induce the invasion of cells in vitro. Mechanically, circ_0008194 presented the binding ability with miR-190a causing the suppression of miR-190a expression, causing the competitive inhibition of AHNAK, resulting in the promotion of EMT. CONCLUSION: Our results suggested that circ_0008194 may act as a sponge to adsorb miR-190a, thereby promoting the expression of AHNAK and promoting the metastasis of liver cancer tumors.

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