RAD51 novel target EIF4A1 promotes colorectal cancer cell proliferation and migration via the CYP51A1/cholesterol metabolic homeostasis pathway

Abstract Colorectal cancer (CRC) is a highly prevalent malignant tumor of the digestive tract worldwide. Although there is indirect evidence suggesting that Eukaryotic translation initiation factor 4A1 (EIF4A1) may be involved in the progression of CRC, its specific regulatory role in the proliferation and migration of CRC cells and the related molecular mechanisms remain unclear at present. This study found that knockdown of EIF4A1 significantly inhibited the proliferation and migration of CRC cells; knockdown of EIF4A1 significantly reduced the intracellular total cholesterol content and the protein expression level of CYP51A1 in CRC cells, and the recombinant protein of CYP51A1 could reverse the reduction effect of knockdown of EIF4A1 on the intracellular total cholesterol content and the inhibition effect on the proliferation and migration of CRC cells; knockdown of RAD51 significantly reduced the expression level of EIF4A1 in CRC cells and there was a RAD51 binding site in the EIF4A1 promoter region, that is, EIF4A1 could be transcribed and activated by RAD51. In summary, this study found that EIF4A1 could promote the proliferation and migration of CRC cells through the CYP51A1/cholesterol metabolic homeostasis pathway under the transcriptional activation effect of RAD51.