Propofol regulates the progression of hepatocellular carcinoma via the POLR2L/TGF-β signaling pathway.

Background: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Propofol has been reported to modulate tumorigenesis in HCC; the aim of this study was to investigate the effect of the interaction of propofol with POLR2L on HCC tumor progression in HCC.
Methods: The propofol-related GSE101724 dataset was analyzed using weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) to identify overlapping genes. Key genes were selected from The Cancer Genome Atlas-liver hepatocellular carcinoma (TCGA-LIHC)-DEGs for prognostic analysis. The impact of POLR2L on LIHC patient survival was assessed, followed by in vitro experiments to validated its effects on HCC cell behavior and signaling pathways.
Results: Fourteen overlapping genes were identified in the turquoise module (highest correlation) of up-regulated DEGs and GSE101724. Further analysis obtained 11 key overlapping genes from 14 overlapping genes and TCGA-LIHC-DEGs, among which HSPE1 and POLR2L showed significant prognostic correlation. Patients with LIHC have a worse chance of surviving when their POLR2L expression is elevated. Knockdown POLR2L significantly inhibited the proliferation, invasion, and migration of HCC cell lines. Downregulation of POLR2L was accompanied by induced apoptosis, cell cycle arrest, and modulation of the expression of apoptosis-related genes. Propofol was found to downregulate POLR2L expression, inhibiting cell proliferation and growth. Further, it was shown that propofol controlled the development of HCC by influencing the POLR2L/TGF-β signaling loop.
Conclusions: The results validated the predictive relevance of POLR2L in HCC and emphasized that propofol can regulate HCC progression through the POLR2L/TGF-β signaling pathway.
Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-2066/coif). The authors have no conflicts of interest to declare.
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