Clinical Pathological Significance and Biological Function of PLIN1 in Hepatocellular Carcinoma: bioinformatics analysis and in vitro experiment

Abstract

Background & aims: Perilipin1 (PLIN1) is an essential lipid droplet surface protein that participates in cell life activities by regulating energy balance and lipid metabolism. PLIN1 has been shown to have a close relationship with the development of numerous tumor types. The purpose of this work is to elucidate the clinicopathologic significance of PLIN1 in hepatocellular carcinoma (HCC), as well as its impact on the biological functions of HCC cells, and investigate possible mechanisms. Methods: Public high-throughput RNA microarray and RNA sequencingwere collected to examine PLIN1 levels and clinical significance in HCC. Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (RT-qPCR) were conducted to assess PLIN1 expression levels and clinicopathological relevance of PLIN1 in HCC. Then, SK and Huh7 cells were transfected with a lentivirus overexpressed PLIN1. CCK8 assay, wound healing assay, transwell assay, and flow cytometric analysis were conducted to explore the effects of PLIN1 overexpression on HCC cell proliferation, migration, invasion, and cell cycle distribution. Ultimately, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the underlying mechanisms of PLIN1 in HCC base on HCC differentially expressed genes and PLIN1 co-expressed genes. Results: PLIN1 was markedly down-regulated in HCC tissues, which correlated with a noticeably worse prognosis for HCC patients. Additionally, PLIN1 overexpression inhibited the proliferation, migration, and invasion in SK and Huh7 cells in vitro, as well as arresting the HCC cell cycle at the G0/G1 phase. More significantly, energy conversion-related biological processes, lipid metabolism, and cell cycle signaling pathways were the three most concentrated molecular mechanisms. Conclusion: The current study found that down-regulated PLIN1 is associated with a poor prognosis in HCC patients and prevented HCC progression by inhibiting cellular proliferation, migration, and metastasis, as well as the mechanisms underlying the regulation of lipid metabolism-related pathways in HCC.