Tripartite Motif Containing 35 (TRIM35) Contributes To The Proliferation, Migration, And Invasion Of Lung Cancer Cells In Vitro And Vivo

Objective:Lung cancer is one of the cancers with the highest morbidity and mortality in the world,but the pathogenesis of lung cancer is still unclear,which is a key issue facing the diagnosis and treatment of lung cancer.Previous studies have shown that members of TRIM family proteins play a crucial role in the development and progression of cancer.So far,only a few TRIM family members have been described in terms of their functions and specific mechanisms.However,TRIM35 has only been studied in a few tumors such as liver cancer and leukemia,and its role in non-small cell lung cancer(NSCLC)remains unclear.Our research aims to reveal the relationship between TRIM35 and NSCLC and provide a theoretical basis for new targets for lung cancer treatment.Method:We verified the expression of TRIM35 gene in tumor databases and clinical samples,and then searched for the effect of TRIM35 on NSCLC in vitro through CCK-8,clone formation experiment,scratch experiment,Transwell experiment,and at the same time studied the effect of TRIM35 in vivo through subcutaneous tumorigenesis experiment.Finally,we use bioinformatics analysis to screen out molecules or pathways that may interact with TRIM35.Result:Our research shown that the expression of TRIM35 in NSCLC tissue samples is increased,and the clinical prognosis of patients with high expression of TRIM35 is poor.Then we selected some of the common lung cancer cell lines(A549,H1299,HCC827,H3122,H460,)and human normal lung epithelial cells HBE,to detect the basic expression of TRIM35,and selected suitable for our knockdown and overexpression cell line.Subsequently,overexpression of TRIM35 promoted cell proliferation,migration and invasion in the H460 cell line,while knocking down TRIM35 in the A549 and H1299 cell lines inhibited cell proliferation,migration and invasion.The tumors of mice overexpressing the TRIM35 group were significantly heavier than control group in animal experiments,it showed that the overexpression of TRIM35 promoted tumor formation.We suspect that TRIM35 promotes migration and invasion of lung cancer cells may be caused by epithelial cell-mesenchymal transition(EMT).We tested the mRNA expression of EMT-related molecules and the results were as expected.Then we screened the differential genes after overexpressing TRIM35 by RNA-seq analysis.After further clustering and cell function and pathway analysis,we found that TRIM35 promotes the proliferation,migration and invasion of lung cancer through the regulation of cancer-related functions and signaling pathways.Conclusion:The research found that the expression of TRIM35 gene is up-regulated in lung cancer and play a certain role in promoting cancer,as well as the relationship between its clinical features,pathological grade and prognosis in non-small cell lung cancer.At the same time,it provides relevant theoretical basis for early screening of lung cancer and observation of therapeutic effects.