LukS-PV Inhibits Hepatocellular Carcinoma Cells Migration via the TNNC1/PI3K/AKT Axis

Purpose: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. LukS-PV is the S component of Panton-Valentine leucocidin (PVL), a toxin secreted by Staphylococcus aureus. We aimed to investigate the role of LukS-PV in HCC cell migration and the specific molecular mechanism involved.

Methods: We used scratch assays to detect the mobility of liver cancer cells treated with LukS-PV. Quantitative real-time PCR and Western blot analysis were performed to detect the expression levels of related genes. RNA sequencing and quantitative proteomics sequencing were used to assess the transcriptional and proteomic alterations of target genes. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) pathway analyses revealed the downstream signaling pathway targets of LukS-PV.

Results: Our results demonstrated that LukS-PV could inhibit HCC cell migration in a concentration-dependent manner. LukS-PV could also downregulate the expression of TNNC1, which was highly expressed in HCC cells. Additionally, the study showed that LukS-PV inhibited HCC cell migration by downregulating TNNC1. Further studies showed that LukS-PV inhibited the phosphorylation of PI3K/AKT pathway by targeting TNNC1, thereby inhibiting HCC cell migration.

Conclusion: Our study demonstrated that LukS-PV has an inhibitory role in the migration of liver cancer cells through the TNNC1/PI3K/AKT axis.