Department of Pathology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou Worker's Hospital, Liuzhou, Guangxi Zhuang Autonomous Region, 545000, People's Republic of China.
Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People's Republic of China.
BMC Cancer. 2024 Aug 30;24(1):1073. doi: 10.1186/s12885-024-12842-1.
BACKGROUND & AIMS: 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.
脂滴包被蛋白 1（PLIN1）是一种重要的脂滴表面蛋白，通过调节能量平衡和脂质代谢参与细胞生命活动。PLIN1 与多种肿瘤类型的发生发展密切相关。本研究旨在阐明 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，并探讨其潜在的作用机制。
收集公共高通量 RNA 微阵列和 RNA 测序数据，以检测 HCC 患者中 PLIN1 水平及临床意义。免疫组织化学（IHC）和实时定量逆转录聚合酶链反应（RT‒qPCR）检测 HCC 中 PLIN1 的表达水平及与临床病理的相关性。然后，通过慢病毒过表达 PLIN1 转染 SK 和 Huh7 细胞。CCK8 实验、划痕愈合实验、Transwell 实验和流式细胞术分析用于研究 PLIN1 过表达对 HCC 细胞增殖、迁移、侵袭和细胞周期分布的影响。最后，根据 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，以探讨 PLIN1 在 HCC 进展中的潜在作用机制。
PLIN1 在 HCC 组织中明显下调，与 HCC 患者的预后明显相关。此外，PLIN1 过表达抑制 SK 和 Huh7 细胞在体外的增殖、迁移和侵袭，并使 HCC 细胞周期停滞在 G0/G1 期。更重要的是，能量转换相关的生物学过程、脂质代谢和细胞周期信号通路是最富集的三个分子机制。
本研究表明，PLIN1 下调与 HCC 患者的不良预后相关，并通过促进细胞增殖、迁移和转移加速 HCC 进展，其作用机制涉及调节 HCC 中脂质代谢相关通路。
