ApoM regulates PFKL through the transcription factor SREBF1 to inhibit the proliferation, migration and metastasis of liver cancer cells

Abstract

Apolipoprotein M (ApoM) is considered a protective factor that inhibits the occurrence and development of liver cancer, but the specific underlying mechanisms require further investigation. Previous studies have demonstrated that ApoM gene knockout promotes the expression of the transcription factor sterol regulatory element-binding protein 1 (SREBP1; also known as SREBF1) in the livers of mice. SREBF1 is closely associated with factors involved in fatty acid synthesis and has a role in the promotion of tumor progression. The present study initially confirmed that the expression levels of ApoM in cancer tissues were significantly decreased compared with those in normal tissue, while the expression levels of SREBF1 were significantly increased. In addition, ApoM gene knockout significantly increased the expression levels of SREBF1 and the key glycolytic enzyme ATP-dependent 6-phosphofructokinase, liver type (PFKL). Binding site prediction and a dual-luciferase reporter gene assay indicated that SREBF1 regulates the promoter region of PFKL. To the best of our knowledge, the present study was the first to propose the regulation of glycolytic enzyme transcription levels by SREBF1. Furthermore, cell proliferation and Transwell assays demonstrated that ApoM gene knockout increased the expression levels of SREBF1 and further enhanced the activity of the promoter region of PFKL, ultimately promoting the proliferation, migration and invasion of liver cancer cells.

Cross talk between genetics and biochemistry in the pathogenesis of hepatocellular carcinoma

“…[ 109 ] ApoM can also suppress tumors by altering glycolysis in liver cancer cells via the SREBP1 pathway. [ 110 ] APOE is reported to be positively correlated with the HCC tumor grade. [ 111 ] Therefore, crosstalk should be considered in terms of discovering synergy among pathways and understanding the holistic effects of metabolic components.…”