肝细胞癌（HCC）是肝癌中最常见的类型。由于HCC的隐匿性起病，早期诊断相对较困难。HCC还表现出对一线治疗药物的强烈抵抗。因此，急需新型精确的HCC诊断和预后生物标志物。我们采用生物信息分析、细胞体外功能实验和裸鼠移植瘤模型来系统研究溶质载体家族37成员3（SLC37A3）在HCC进展中的作用。首先，生物信息学分析表明，与正常组织相比，HCC组织中SLC37A3的表达显著增加。SLC37A3的表达还与肿瘤分期和各种临床和病理特征有关。通过细胞内免疫组织化学实验验证HCC细胞中SLC37A3表达呈类似趋势。接下来的生存分析表明，相比于SLC37A3表达低的HCC患者，表达高的HCC患者的总体、1年、3年和5年生存率均降低了。裸鼠移植瘤实验也表明，SLC37A3的沉默显著抑制了HCC的肿瘤发生。细胞功能实验表明，SLC37A3的沉默抑制了HCC细胞增殖和转移，同时促进细胞凋亡。此外，SLC37A3-knockdown HCC细胞的RNA-seq分析表明，1型糖尿病（T1DM）相关信号通路显著改变。胰岛素分泌相关和糖酵解/糖异生相关基因的表达水平也发生了改变，表明SLC37A3可能参与了葡萄糖代谢的调节。总之，SLC37A3代表了一种前景广阔的HCC诊断和预后生物标志物，其功能在于调节葡萄糖代谢。 版权所有©2023 Elsevier B.V.。

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Due to the insidious onset of HCC, early diagnosis is relatively difficult. HCC also exhibit strong resistance to first-line therapeutic drugs. Therefore, novel precise diagnostic and prognostic biomarkers for HCC are urgently needed. We employed a combination methods of bioinformatic analysis, cell functional experiments in vitro and a xenograft tumour model in vivo to systematically investigate the role of solute carrier family 37 member 3 (SLC37A3) in HCC progression. First, bioinformatic analysis demonstrated that SLC37A3 expression was significantly increased in HCC tissues compared with normal tissues. SLC37A3 expression was also associated with tumour stages and various clinical and pathological features. Similar trends in SLC37A3 expression levels were verified in HCC cells and by using IHC experiments. Next, survival analysis showed that the overall, 1-year, 3-year and 5-year survival rates were decreased in HCC patients with high SLC37A3 expression compared with HCC patients low SLC37A3 expression. Xenograft tumour experiments also suggested that SLC37A3 knockdown significantly inhibited HCC tumourigenesis in vivo. Cell functional experiments suggested that SLC37A3 knockdown inhibited HCC cell proliferation and metastasis, but promoted apoptosis. Furthermore, RNA-seq analysis of SLC37A3-knockdown HCC cells indicated that the type 1 diabetes mellitus (T1DM)-related signalling pathway was significantly altered. The expression levels of insulin secretion-related and glycolysis/gluconeogenesis-related genes were also altered, suggesting that SLC37A3 might be involved in the regulation of glucose homeostasis. In summary, SLC37A3 represents a prospective diagnostic and prognostic biomarker for HCC that functions in glucose metabolism regulation.Copyright © 2023 Elsevier B.V. All rights reserved.