New use of an old drug: mechanism of oseltamivir phosphate inhibiting liver cancer through regulation of lipophagy via NEU1

Neuraminidase-1 (NEU1) is an enzyme that breaks down sialic acids on glycoproteins and glycolipids. Aberrant expression of NEU1 has been linked to the progression of numerous malignancies, including liver cancer. Oseltamivir phosphate (OP) is a drug used to treat and prevent influenza, which specifically inhibits NEU1. However, the molecular mechanisms of NEU1 in liver cancer and the potential therapeutic effects of OP remain largely unclear.NEU1 expression in liver cancer was evaluated using public databases and validated in our samples. CRISPR/Cas9, CCK-8 assay, transwell assays, oil red O staining, RNA-sequencing, immunofluorescence and co-immunoprecipitation (Co-IP) and in vivo experiments were used to investigate the biological function of NEU1 and the therapeutic effect of OP in liver cancer.

神经氨酸酶-1（Neuraminidase-1, NEU1）是一种可降解糖蛋白与糖脂表面唾液酸的酶。NEU1的异常表达与包括肝癌在内的多种恶性肿瘤的进展密切相关。磷酸奥司他韦（Oseltamivir phosphate, OP）是一款用于治疗和预防流感的药物，可特异性抑制NEU1的活性。然而，目前NEU1在肝癌中的分子机制以及OP的潜在治疗效应仍尚未完全明确。本研究首先通过公共数据库对肝癌组织中的NEU1表达水平进行评估，并在本课题组的临床样本中完成验证。随后采用CRISPR/Cas9基因编辑技术、CCK-8细胞增殖实验、Transwell实验、油红O染色、RNA测序、免疫荧光染色、免疫共沉淀（Co-immunoprecipitation, Co-IP）以及体内实验等多种实验手段，探究NEU1在肝癌中的生物学功能以及OP的治疗效果。