Transcription Factor TCF12 Activates the Transcription Level of SLC38A1 to Promote the Development of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. The pathogenic mechanism of HCC is complex. In this study, we aimed to explore the functions of Solute Carrier Family 38 Member 1 (SLC38A1) and transcription factor 12 (TCF12) in HCC malignancy. Immunohistochemistry (IHC) assay was performed to estimate the expression of SLC38A1 in HCC. qRT-PCR assay and western blot assay were conducted to determine the expression of SLC38A1, TCF12, epithelial-mesenchymal transition (EMT)-related markers and ferroptosis-related markers. Colony formation assay and EdU assay were utilized to evaluate cell proliferation ability. Transwell assay was employed for cell migration and invasion. Reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and iron levels were examined with related kits. ChIP assay and dual-luciferase reporter assay were performed to verify the relationship between TCF12 and SLC38A1. The in vivo experiment was conducted to assess the function of TCF12 in vivo. SLC38A1 was upregulated in HCC tissues and cells. SLC38A1 knockdown suppressed HCC cell proliferation, migration, invasion, and EMT and inhibited ferroptosis in vitro. The transcription factor TCF12 could activate the transcription level of SLC38A1. TCF12 overexpression ameliorated the effects of SLC38A1 knockdown on HCC cell malignant behaviors. Moreover, TCF12 silencing inhibited tumorigenesis in vivo. TCF12 targeted SLC38A1 to promote HCC cell proliferation, migration and invasion and restrained ferroptosis, providing a novel sight for HCC pathogenesis.