C-Myc Promotes Cholesterol Synthesis And Cell Proliferation Through Transcriptional Activation Of SQLE

The protein C-Myc expressed by C-Myc oncogenes is a very important transcription factor,which can regulate about 10-15%of the human genome by assembling transcription complexes with the Max protein.C-Myc can be involved in regulating the expression of genes related to cell growth and cell metabolism to promote cell growth and proliferation.A number of studies have shown that abnormal amplification and expression of C-Myc can promote the development of many human tumors.Cholesterol metabolism provides an indispensable component of cell membrane and many important metabolic intermediates to support cell growth.Abnormal rapid proliferation of tumor cells requires a large amount of cholesterol to meet the rapid division and proliferation of cells.Therefore,cholesterol metabolism plays a very necessary role in tumor cells.However,so far,the mechanism of how cholesterol biosynthesis is accurately regulated to promote tumorigenesis and development is still unclear,and the regulatory mechanism of C-Myc in cholesterol metabolism is not clear.Therefore,we explored this.We found that using siRNAs and overexpression plasmids to change the expression of C-Myc in tumor cells could significantly affect the intracellular cholesterol biosynthesis and the viability and proliferation of tumor cells.Then we found that using siRNAs and overexpression plasmids to change the expression of C-Myc in tumor cells could significantly affect the mRNA and protein levels of squalene monooxygenase,SQLE,one of the two rate-limiting enzymes in cholesterol biosynthesis pathway.Through further luciferase reporter gene experiment and CHIP experiment,we found that C-Myc could increase cholesterol production and promote tumor cell proliferation by direct transcriptional upregulation SQLE,and SQLE overexpression could restore cholesterol levels in C-Myc knockdown cells.More importantly,in SQLE knockdown cells,overexpression of C-Myc didn't enhance intracellular cholesterol levels.Therefore,our results suggest that C-Myc promote cholesterol synthesis and cell proliferation by direct transcriptional upregulation SQLE.