Glypican-3 knockdown inhibits the cell growth, stemness, and glycolysis development of hepatocellular carcinoma cells under hypoxic microenvironment through lactylation.

IF 2.5 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Archives of Physiology and Biochemistry Pub Date : 2024-10-01 Epub Date: 2023-05-02 DOI:10.1080/13813455.2023.2206982

Gebing Yao, Zihua Yang

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引用次数: 0

Abstract

Context: Hepatocellular carcinoma (HCC) is a common malignant tumour in China. Glypican-3 (GPC3) is reported to be closely related to the occurrence and development of various tumours.

Objective: This study aimed to explore the role of GPC3 in HCC.

Materials and methods: The cell behaviours were investigated using Cell Counting Kit-8 (CCK-8), Traswell, and sphere formation assays. The protein and mRNA expression levels were detected using western blot and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) assays.

Results: The results showed that GPC3 knockdown decreased the cell viability and stemness, glucose uptake, lactate production, and extracellular acidification rate (ECAR), while increased the oxygen consumption rate (OCR) in hypoxia-treated HCC cells. Additionally, GPC3 knockdown decreased the global lactylation and c-myc lactylation, which further decreased the protein stability and expressions of c-myc.

Discussion and conclusion: GPC3-mediated lactylation modification may be a new direction in HCC treatment in the future.

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敲除 Glypican-3 可通过乳化作用抑制缺氧微环境下肝癌细胞的生长、干性和糖酵解发育。

背景：肝细胞癌（HCC）是中国常见的恶性肿瘤。据报道，Glypican-3（GPC3）与多种肿瘤的发生和发展密切相关：本研究旨在探讨 GPC3 在 HCC 中的作用：采用细胞计数试剂盒-8（CCK-8）、Traswell和球形成试验研究细胞行为。采用 Western 印迹和实时定量聚合酶链反应（RT-qPCR）检测蛋白质和 mRNA 的表达水平：结果表明，在缺氧处理的 HCC 细胞中，GPC3 基因敲除降低了细胞活力和干性、葡萄糖摄取、乳酸生成和细胞外酸化率（ECAR），同时提高了耗氧率（OCR）。此外，GPC3敲除降低了全局乳化和c-myc乳化，从而进一步降低了c-myc的蛋白稳定性和表达量：GPC3介导的乳化修饰可能是未来治疗HCC的一个新方向。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY

CiteScore

6.90

自引率

3.30%

发文量

期刊介绍： Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.