Actin-related protein 6 regulates the Hedgehog signaling pathway: Molecular basis for stemness maintenance of hepatoma cells.

[OBJECTIVE] The liver is a common primary cancer site in humans. Actin-related protein 6 (ACTR6) plays a key role in liver cancer. The aim of this study was to further explore the regulatory molecular mechanism of ACTR6 in liver cancer.

[MATERIAL AND METHODS] In this study, hepatoma cell HuH-7 was evaluated by 5-ethynyl-2'-deoxyuridine staining, colony formation, Transwell assay, and wound healing assay. The possible mechanism of the action of ACTR6 on hepatocellular carcinoma cells was evaluated by analyzing sphere formation, the key factors of the Hedgehog (Hh) signaling pathway, and molecules related to cell stemness. Then, xenografted mouse tumor models were used to demonstrate the promotion effect of ACTR6 on liver cancer .

[RESULTS] ACTR6 was highly expressed in HuH-7h and HepG2 cells ( < 0.001). Silencing ACTR6 inhibited the migration, invasion capacity, and activity of HuH-7 ( < 0.01). ACTR6 activated the Hh signaling pathway by upregulating the expression of Sonic Hedgehog, patched 1, smoothened, and glioma-associated transcription factor 1. In addition, ACTR6 increased the molecular level of cell stemness by increasing the level of cellular myelocytomatosis oncogene, octamer-binding transcription factor 4, Nanog homeobox, and SRY-box transcription factor 2. Vismodegib reversed the promoting effect of ACTR6 on the Hh signaling pathway and stem-related proteins in cells.

[CONCLUSION] ACTR6 regulates the molecular basis of stemness maintenance of liver cancer cells through the Hh signaling pathway and promotes the occurrence of liver cancer. This study provides possible targets for the clinical treatment of liver cancer.