PLIN1在肝细胞癌中的临床病理意义和生物学功能:生物信息学分析和体外实验。
Clinical pathological significance and biological function of PLIN1 in hepatocellular carcinoma: bioinformatics analysis and in vitro experiments.
发表日期:2024 Aug 30
作者:
Jiang-Hua Huang, Yan Wei, Zhen Fang, Cong Yu, Rui Zhang, Zhen-Bo Feng, Li-Ping Zeng
来源:
GENES & DEVELOPMENT
摘要:
Perilipin 1 (PLIN1) 是一种必需的脂滴表面蛋白,通过调节能量平衡和脂质代谢参与细胞生命活动。 PLIN1已被证明与多种肿瘤类型的发展密切相关。本工作的目的是阐明PLIN1在肝细胞癌(HCC)中的临床病理意义及其对HCC细胞生物学功能的影响,并探讨其潜在机制。公共高通量RNA微阵列和RNA测序收集数据以检查 HCC 患者的 PLIN1 水平和临床意义。采用免疫组织化学 (IHC) 和实时定量逆转录聚合酶链反应 (RT-qPCR) 来评估 HCC 中 PLIN1 的表达水平和临床病理相关性。然后,用过表达 PLIN1 的慢病毒转染 SK 和 Huh7 细胞。通过CCK8实验、伤口愈合实验、Transwell实验和流式细胞术分析PLIN1过表达对HCC细胞增殖、迁移、侵袭和细胞周期分布的影响。最终,基于HCC差异表达基因和PLIN1共表达基因,进行基因本体论(GO)功能注释和京都基因与基因组百科全书(KEGG)通路分析,以研究PLIN1在HCC进展中的潜在机制。PLIN1显着下调在 HCC 组织中,这与 HCC 患者的预后明显较差相关。此外,PLIN1过表达在体外抑制SK和Huh7细胞的增殖、迁移和侵袭,并将HCC细胞周期阻滞在G0/G1期。更重要的是,能量转换相关的生物过程、脂质代谢和细胞周期信号通路是三个最丰富的分子机制。本研究表明,PLIN1 下调与 HCC 患者预后不良相关,并通过促进细胞增殖、加速 HCC 进展、迁移、转移,以及 HCC 脂质代谢相关途径的调节机制。© 2024。作者。
Perilipin 1 (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 be closely related to the development of numerous tumor types. The purpose of this work was to elucidate the clinicopathologic significance of PLIN1 in hepatocellular carcinoma (HCC), as well as its impact on the biological functions of HCC cells, and to investigate the underlying mechanisms involved.Public high-throughput RNA microarray and RNA sequencing data were collected to examine PLIN1 levels and clinical significance in patients with HCC. Immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction (RT‒qPCR) were conducted to assess the expression levels and the clinicopathological relevance of PLIN1 in HCC. Then, SK and Huh7 cells were transfected with a lentivirus overexpressing 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 progression based on HCC differentially expressed genes and PLIN1 co-expressed genes.PLIN1 was markedly downregulated in HCC tissues, which correlated with a noticeably worse prognosis for HCC patients. Additionally, PLIN1 overexpression inhibited the proliferation, migration, and invasion of 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 signalling pathways were the three most enriched molecular mechanisms.The present study revealed that PLIN1 downregulation is associated with poor prognosis in HCC patients and accelerated HCC progression by promoting cellular proliferation, migration, and metastasis, as well as the mechanisms underlying the regulation of lipid metabolism-related pathways in HCC.© 2024. The Author(s).