Trp14 Promotes Proliferation And Invasion Of Non-small Cell Lung Cancer By Regulating Autophagy

Lung cancer is the most common malignant tumor and the tumor that causes the most deaths among cancer patients.Although in the past few decades,the treatment of lung cancer has made great progress,due to the role of epigenetic and other complex factors in tumor growth and invasion,the long-term survival rate of patients is still not high.Therefore,revealing the molecular mechanism of lung cancer invasion and metastasis and finding new biological markers of lung cancer will not only be of great benefit to the treatment of lung cancer,but also provide an experimental basis for the development of effective targeted therapy drugs.Thioreductin-related protein 14(Trp14)is a highly conserved disulfide bond reductase with a molecular weight of 14 k Da,and is an evolutionarily conserved member of the thioredoxin(Trx)family.The sulfur redox protein system is an important redox response regulation system in the body.In addition to inhibiting oxidative stress,it also has a variety of biological functions such as regulating cell growth,energy metabolism and signal transduction.In recent years,it has been found that Trp14 promotes resistance to paclitaxel in ovarian cancer and neuroblastoma by inducing autophagy.So,whether sulfur redox protein-related protein 14 can affect non-small cell lung cancer by inducing autophagy has aroused our interest.In this article,we detected the expression level of Trp14 in lung cancer cell lines and lung cancer resection specimens,analyzed the relationship between patient clinical progress and prognosis,and observed the effect of overexpression of Trp14 on the proliferation and invasion of non-small cell lung cancer and the regulation of autophagy by Trp14 on lung cancer cells.Objective:To explore the expression of Thioredoxin-related protein of 14 k Da(Trp14)in non-small cell lung cancer(NSCLC)in vitro,its clinicopathological significance,its proliferation and the impact of invasion and the regulation of autophagy.Methods:1.Analyze the expression of Trp14 in lung cancer tissues and its relationship with clinicopathological factors by immunohistochemistry.2.Observe the effect of overexpression of Trp14 on the biological function of proliferation and invasion of lung cancer cell through experimental methods such as colony formation and transwell.3.Observe the effect of regulating the expression of Trp14 on the expression of autophagy-related genes by Western Blot.Results : 1.Immunohistochemical staining to detect the expression of Trp14 in normal tissues and tumor tissues.Trp14 immunostaining was weak in normal lung tissue,with a positive rate of 7.5%(3/40)(p<0.05).The positive rate of Trp14 in lung cancer tissue was 59.8%(61/102)(p<0.05),which was significantly higher than that in normal lung tissue.The statistical results show that the high expression of Trp14 is related to poor differentiation of lung cancer(p<0.05),high TNM stage(p<0.05)and lymph node metastasis(p<0.05).Survival analysis showed that the survival time of patients with high Trp14 expression was significantly shorter than the p-value of patients with low expression(p<0.05).2.The Trp14 overexpression plasmid was transfected into A549 and H1299 cell lines,and it was found that overexpression of Trp14 significantly promoted the proliferation and invasion of lung cancer cells(p<0.05).3.Trp14 overexpressed in A549 and H1299 cell lines,and Beclin1 expression was found to be up-regulated(p<0.05).4.Trp14 promotes non-small cell lung cancer by inducing autophagy.After overexpression of Trp14,adding autophagy inhibitor Baf-A1,Trp14 regulates the proliferation and invasion of NSCLC is inhibited(p<0.05),suggesting that Trp14 promotes the proliferation and invasion of non-small cell lung cancer by inducing autophagy.Conclusion:1.Trp14 is highly expressed in NSCLC,and its overexpression is related to NSCLC differentiation,TNM staging,lymph node metastasis and patient prognosis.2.Overexpression of Trp14 can promote the proliferation and invasion of non-small cell lung cancer cells.3.Trp14 promotes the proliferation and invasion of non-small cell lung cancer cells by regulating autophagy.