LncRNAs play crucial roles in the development of various cancers including hepatocellular carcinoma (HCC). Nevertheless, the function of the long noncoding RNA (lncRNA) FOXD2‐AS1 in HCC is still poorly understood. In this study, we focused on the role of FOXD2‐AS1 in HCC. We found that FOXD2‐AS1 was significantly upregulated in HCC cells in comparison to normal human liver cells, LO2. In this study, we also demonstrated that miR‐206 expression was greatly reduced in HCC cells. Furthermore, the inhibition of FOXD2‐AS1 repressed HCC cell proliferation, enhanced cell apoptosis, and restrained cell invasion and migration. The knockdown of FOXD2‐AS1 elevated miR‐206 expression, and we validated an interaction between these RNAs. Additionally, miR‐206 mimics inhibited HCC development while miR‐206 mimics had the opposite effect. MAP kinase 1 (MAP3K1) was predicted to be a target of miR‐206. We discovered that FOXD2‐AS1 modulated MAP3K1 expression by sponging miR‐206 in MHCC‐97L and HepG2 cells. Finally, our in vivo experiments validated that the knockdown of FOXD2‐AS1 inhibited HCC progression by modulating the miR‐206/MAP3K1 axis. In conclusion, this work implies FOXD2‐AS1 accelerates HCC progression through sponging miR‐206 and regulating MAP3K1 expression.
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