Regulatory Mechanisms Of TFAP2A In Promoting Esophageal Cancer Cell Proliferation And The Ferroptosis Of Esophageal Cancer Cells

Esophageal cancer is a common malignant tumor of the digestive tract in humans.According to the pathological type,it is mainly divided into two types: esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC).China is a high incidence area of esophageal cancer,mainly squamous cell carcinoma,with high mortality and poor prognosis.Therefore,identifying key driver genes in the progression of esophageal cancer and revealing its regulatory mechanism will help elucidate the carcinogenic mechanism of esophageal cancer,provide candidate molecular markers for esophageal cancer screening and diagnosis,and provide candidate molecular targets for esophageal cancer treatment point.The transcription factor TFAP2 A is expressed early in embryogenesis and is abnormally highly expressed in various tumors.Studies have reported that TFAP2 A can play a role in tumor progression by regulating the cell cycle,epithelial-mesenchymal transition(EMT)and apoptosis.Early laboratory research found that TFAP2 A in esophageal cancer is regulated by super enhancers.This paper found that knockdown TFAP2 A significantly inhibited the proliferation and cloning ability of esophageal cancer cells KYSE140,KYSE510 and KYSE70.This result indicates that the transcription factor TFAP2 A activated by super-enhancer in esophageal cancer plays a role in promoting tumor cell proliferation.Ferroptosis is a newly discovered iron-dependent programmed cell death pathway,mainly caused by the accumulation of reactive oxygen species(ROS),which is different from apoptosis and necrosis.Glutathione peroxidase(GPX4)can convert lipid peroxides to inert lipid alcohols,so it plays an important antioxidant role in cells.The solute carrier family 7 member 11(SLC7A11)is a member of the cystine / glutamic acid transport system(system XC-).It is located at the plasma membrane and participates in the transmembrane transport of cystine.It is essential to maintain the redox balance in the cell.The current study found that GPX4 and SLC7A11 are the key regulatory genes in the process of cell ferroptosis.More and more studies have found that ferroptosis inducers have a strong effect of inhibiting tumor growth and increasing the sensitivity of chemotherapy.In this paper,the ferroptosis inducer RSL3 is used to construct an ferroptosis model of esophageal cancer cells,and then RNA-seq technology is used to screen and identify key genes in the process of ferroptosis of esophageal cancer cells.The results showed that the expression of ASPM,TOP2 A,and CENPF were down-regulated after RSL3 induced ferroptosis in esophageal cancer cells,and silencing ASPM,TOP2 A,and CENPF increased the sensitivity of esophageal cancer cells to RSL3-induced ferroptosis.At the same time,we found that after silencing ASPM,TOP2 A and CENPF,GPX4 protein was significantly down-regulated,while SLC7A11 had no significant changes.This result indicates that ASPM,TOP2 A,and CENPF can regulate GPX4 during the process of ferroptosis of esophageal cancer cells.In conclusion,the results of this paper reveal the promoting effect of TFAP2 A on the proliferation of esophageal cancer cells,and identify the regulatory genes in the process of ferroptosis of esophageal cancer cells,which will provide a theoretical basis for the clarification of the carcinogenic mechanism of esophageal cancer in the future.