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.