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Abstract 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.

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. [ABSTRACT FROM AUTHOR]

miR-206 plays an important role in regulating the growth of multiple cancer cells. Cyclin-dependent kinase 9 (CDK9) stimulates the production of abundant prosurvival proteins, leading to impaired apoptosis of cancer cells. However, it is unknown whether CDK9 is involved in the miR-206-mediated growth suppression of hepatocellular carcinoma (HCC) cells. In this study, we found that the expression level of miR-206 was significantly lower in HCC cell lines than that in normal hepatic cell line (L02). Meanwhile, CDK9 was upregulated in HCC cell lines. Moreover, miR-206 downregulated CDK9 in HCC cells via directly binding to its mRNA 3′ UTR, which resulted in a decrease of RNA PolII Ser2 phosphorylation and Mcl-1 level. Additionally, miR-206 suppressed the cell proliferation, and induced cell cycle arrest and apoptosis. Similarly, silence or inhibition of CDK9 also repressed the cell proliferation, and induced cell cycle arrest and apoptosis. Taken together, the results demonstrated that miR-206 inhibited the growth of HCC cells through targeting CDK9, suggesting that the miR-206-CDK9 pathway may be a novel target for the treatment of HCC. [ABSTRACT FROM AUTHOR]