Impact of SLC-0111 (U-104) on HUH6 hepatoblastoma cell transcriptome in normoxic and hypoxic conditions

Carbonic anhydrase 9 (CAIX) is a transmembrane metalloenzyme whose main function is to maintain the acid-base balance of the cell and hypoxic condition induces its expression. Solid tumors often exhibit regions with low oxygen content in areas where the blood supply is insufficient. CAIX is overexpressed in multiple solid tumors, including hepatoblastoma, the most frequent childhood liver malignancy. SLC-0111 is a commercially available CAIX inhibitor that is currently passed Phase I clinical trial on solid tumors. In this study we assessed the impact of SLC-0111 on transcriptomic changes of HUH6 hepatoblastoma cell line cells in both normoxic and hypoxic condition. Overall design: HUH6 cells were treated with CAIX/XII inhibitor SLC-0111 (U-104) under normoxic or hypoxic conditions for 48 h. Cells were lysed and RNA was extracted. RNA sequencing was utilized to define transcriptomic changes caused by SLC-0111 treament in normoxia and hypoxia. In each group, four technical replicates were sequenced.

碳酸酐酶9（Carbonic anhydrase 9, CAIX）是一种跨膜金属酶，其核心功能为维持细胞酸碱平衡，缺氧条件可诱导其表达。实体瘤常于血供不足区域形成低氧微环境。CAIX在多种实体瘤中呈过表达状态，其中包括儿童最常见的肝脏恶性肿瘤——肝母细胞瘤。SLC-0111是一款市售的CAIX抑制剂，目前已完成实体瘤相关的I期临床试验。本研究旨在评估SLC-0111对常氧及缺氧条件下肝母细胞瘤HUH6细胞系转录组变化的影响。
实验整体设计：将HUH6细胞于常氧或缺氧环境中，经CAIX/XII抑制剂SLC-0111（U-104）处理48小时；随后裂解细胞并提取总RNA，采用RNA测序技术分析常氧与缺氧条件下SLC-0111处理所诱导的转录组变化。每组设置4个技术重复样本进行测序。