Loss of TPC2 and TRPML1 on gene expression of hepatocellular carcinoma

To investigate the transcriptional impact of lysosomal ion channels in cancer, we performed RNA sequencing on wild-type (WT), TPC2 knockout (KO), and TRPML1 KO hepatocellular carcinoma (HCC) cell lines RIL175 and Hep3B. Transcriptomic analysis revealed that TPC2 ablation leads to pronounced alterations in tumor cell metabolism, including significant downregulation of genes involved in amino acid biosynthesis and glycolysis. These changes were specific to TPC2 KO cells and were not observed in TRPML1 KO cells. Thus, RNA sequencing highlights a distinct and critical role for TPC2 in regulating metabolic gene expression, distinguishing its function from other lysosomal ion channels in the same cellular context.

为探究溶酶体离子通道（lysosomal ion channels）对癌症的转录调控影响，我们对野生型（wild-type, WT）、TPC2基因敲除（TPC2 knockout, KO）及TRPML1基因敲除（TRPML1 KO）的肝细胞癌（hepatocellular carcinoma, HCC）细胞系RIL175与Hep3B开展了RNA测序（RNA sequencing）实验。转录组学分析（transcriptomic analysis）结果表明，TPC2基因敲除会导致肿瘤细胞代谢发生显著改变，包括氨基酸生物合成与糖酵解相关基因的显著下调。此类变化仅特异性出现于TPC2 KO细胞中，在TRPML1 KO细胞中未观察到类似改变。综上，RNA测序结果揭示了TPC2在调控代谢基因表达方面具有独特且关键的作用，明确区分了其与同一细胞环境中其他溶酶体离子通道的功能差异。