Ligand-activated PPAR delta expression promotes hepatocellular carcinoma progression by regulating the PI3K-AKT signaling pathway

Background: Peroxisome proliferator-activated receptor-beta/delta (PPAR delta) was considered as the key regulator involved in the evolution of various tumors. Given that PPAR delta potential role in hepatocellular carcinoma (HCC) is still obscure, we comprehensively assessed its expression pattern, prognosis, functions and correlation with tumor microenvironment in HCC using public database data and in vitro studies. Methods: Transcriptional data and clinical data in the TCGA and GEO database were analyzed in R software. Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry were used to detect the expression level of related RNA and proteins. The malignant biological characteristics were explored by cell counting Kit-8 (CCK8), 5-Ethynyl-2MODIFIER LETTER PRIME-deoxyuridine (EdU) assay and wound healing assay. Results: Our results illustrated that PPAR delta expression was significantly higher in HCC tissues and HCC cell lines. Elevated expression of PPAR delta suggested poor clinical staging and prognosis in HCC. Ligand-activated PPAR delta expression promoted the proliferation and invasion of HCC cells via PDK1/AKT/GSK3 beta signaling pathway. The expression of PPAR delta was closely related to the HCC tumor microenvironment. Conclusions: PPAR delta plays an important part in HCC progression, penetrating investigation of the related regulatory mechanism may shed light upon further biological and pharmacological value.

Automated summary

This study comprehensively analyzed data from public databases and conducted laboratory experiments to investigate the role of PPAR delta in hepatocellular carcinoma (HCC). The results showed that PPAR delta expression was significantly elevated in HCC tissues and cell lines and was associated with poor prognosis and malignant biological characteristics. Activation of PPAR delta promoted the proliferation and invasion of HCC cells through a specific signaling pathway. The study also found a close correlation between PPAR delta expression and the HCC tumor microenvironment.