Propofol Inhibits Biological Function of Hepatocellular Carcinoma Cells through LINC00475-Mediated Sonic Hedgehog Pathway

Introduction: Hepatocellular carcinoma (HCC) is the most deadly cancer. Many signal pathways are implicated in HCC development, including sonic hedgehog (SHH). Propofol is an anesthetic commonly used in surgery. Recent studies have reported that propofol inhibits tumorigenesis and the development of HCC in a dose-dependent manner. The study aimed to identify the mechanism of how the propofol-mediated SHH-signaling molecule works in HCC. Methods: Cell proliferation, apoptosis, and invasion were examined, respectively, through colony formation, TUNEL, caspase-3 activity, and transwell assays. Protein levels of SHH, Ptch1, Smo, and Gli1 were determined via Western blot. Results: Propofol could inhibit cell proliferation, migration, and invasion and induce apoptosis via suppression on SHH to inactivate the SHH pathway. By mechanistic assays, miR-340-5p was identified to target SHH and negatively regulate SHH. Long intergenic non-protein coding RNA 475 (LINC00475) was the endogenous sponge of miR-340-5p to upregulate SHH. Finally, the rescue assays were implemented. The activator of the SHH pathway completely rescued the effects of LINC00475 and SHH in propofol-induced HCC cells. Conclusion: Propofol inhibits HCC cell malignant behaviors via repressing LINC00475 to suppress SHH, thus inactivating the SHH pathway. These new findings might contribute to the understanding and application of propofol in HCC.