Study On The Mechanisms Of Human Peptide Deformylase Promoting Colorectal Cancer Cell Proliferation

Cancer is one of the leading causes of human death in the world today.China has a large number of cancer patients and is a country with high cancer rate in the world.In recent years,due to the influence of various internal and external factors,the incidence of cancer patients with younger age and the incidence of cancer and mortality are soaring.Due to the lack of effective treatments for cancer and the high cost of treatment,which causes a heavy burden to society and families,it is urgent to study the mechanism of tumor formation and discover new therapeutic targets to develop new anti-tumor drugs.Previous studies in our laboratory have found that Homo sapiens Peptide Deformylase(HsPDF)is closely related to colorectal cancer,but the mechanism of HsPDF in regulating tumors is still unclear.Therefore,in this project,further studies were performed on the mechanism of HsPDF in promoting colorectal cancer cell proliferation so as to find some new biological evidence for HsPDF as an anti-tumor target.HsPDF is a mitochondrial protein,so the effects of regulating HsPDF expression on mitochondrial morphological structure,function and protein expression were systematically investigated.The ultrastructure of mitochondria was observed by transmission electron microscopy,and it was found that the number of HCT116/PDF mitochondria increased and the size increased in overexpressing cells,but the mitochondrial cristae were abnormal.Mitochondria are the main site of ATP production in cells,and we found that HsPDF overexpression induced ATP production in colorectal cancer cells by ATP assay kit.Using the Seahorse Cell Energy Metabolism Analyzer,the relationship between HsPDF and mitochondrial energy metabolism in colorectal cancer cells was preliminarily studied,and it was found that HCT116 cells and HT29 cells with higher HsPDF expression had decreased oxidativephosphorylation levels and increased glycolysis levels,consistent with the "Warburg effect".In addition analysis of mitochondria-encoded proteins revealed that the expression of ATP8 and Cytochrome b was positively correlated with HsPDF.These results suggested that altering the expression of cellular HsPDF affected mitochondrial morphology,energy production,and protein expression,which may mediate the regulation of HsPDF on colorectal cancer cell proliferation and migration.In this study,we found that decreased expression of HsPDF inhibited the proliferation and migration of colorectal cancer cells,and the expression of HsPDF affected CREB protein phosphorylation,Akt/mTOR signaling pathway and mitochondrial morphological structure and function of colorectal cancer cells,but the exact mechanism still needs to be further studied.This study lays a foundation for revealing the mechanism of HsPDF in promoting colorectal cancer cell proliferation and confirming that HsPDF becomes a new drug target and providing new ideas for the development of novel anti-colorectal cancer drugs.