LncRNA FGD5-AS1 Facilitates Hepatocellular Carcinoma Cell Stemness by Enhancing PKD1 mRNA Stability Through Binding With MSI2.

Abstract

Hepatocellular carcinoma (HCC) is a major global health concern that accounts for more than 80% of all primary hepatic carcinomas. The long noncoding RNA FGD5 antisense RNA 1 (FGD5-AS1) has been linked to HCC cell stemness and proliferation. However, the exact function of FGD5-AS1 in HCC remains unclear. Cell viability and proliferation were examined using the CCK8 and colony formation assays, respectively. Cell stemness was examined using a sphere formation assay. To investigate the relation between Musashi 2 (MSI2) and FGD5-AS1 (or protein kinase D1 [PKD1]), RNA immunoprecipitation and RNA pull-down assays were used. Furthermore, a xenograft mouse model was established to evaluate the function of FGD5-AS1 in vivo. FGD5-AS1, MSI2, and PKD1 were upregulated in the HCC tissues. FGD5-AS1 knockdown significantly inhibited the viability, proliferation, and stemness of HCC cells and decreased the expression of MSI2, PKD1, octamer-binding transcription factor 4, SOX2, NANOG, and Prominin-1 in HCC cells. Mechanistically, FGD5-AS1 increased PKD1 mRNA stability by upregulating MSI2 expression. Both MSI2 and PKD1 ameliorated sh-FGD5-AS1's inhibition of HCC cell viability, proliferation, and stemness. Furthermore, FGD5-AS1 silencing inhibited HCC tumor growth and stemness in vivo. FGD5-AS1 promotes the stemness of HCC cells by activating the MSI2/PKD1 axis. Our study provides a new theoretical foundation for the development of novel HCC treatments.