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

Authors :
Wei Han
Nan Wang
Rui Kong
Wen Bao
Jie Lu
Source :
Journal of Translational Medicine, Vol 20, Iss 1, Pp 1-14 (2022)
Publication Year :
2022
Publisher :
BMC, 2022.

Abstract

Abstract Background Peroxisome proliferator-activated receptor-beta/delta (PPARδ) was considered as the key regulator involved in the evolution of various tumors. Given that PPARδ 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-2ʹ-deoxyuridine (EdU) assay and wound healing assay. Results Our results illustrated that PPARδ expression was significantly higher in HCC tissues and HCC cell lines. Elevated expression of PPARδ suggested poor clinical staging and prognosis in HCC. Ligand-activated PPARδ expression promoted the proliferation and invasion of HCC cells via PDK1/AKT/GSK3β signaling pathway. The expression of PPARδ was closely related to the HCC tumor microenvironment. Conclusions PPARδ plays an important part in HCC progression, penetrating investigation of the related regulatory mechanism may shed light upon further biological and pharmacological value.

Details

Language :
English
ISSN :
14795876
Volume :
20
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Translational Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.98b4c00baee47f5b11927c8e03c3715
Document Type :
article
Full Text :
https://doi.org/10.1186/s12967-022-03288-9