Significance Of Expression Of Transcription Factor FOXM1 In Childhood Malignant Solid Tumors

Objective Pediatric malignant tumors are rare diseases in children and the second leading cause of death in children.The incidence of malignant tumors in children aged 0-14 has risen from 116/1000,000 in 1975 to 160/1000,000 in 2017,showing a gradual increase.the trend of.Surgical resection is one of the most commonly selected treatment methods,but the treatment effect is not ideal for children with advanced and metastatic disease.Therefore,further exploration of its molecular mechanism is of great significance for early diagnosis and better treatment strategies.The main purpose of this study is to investigate the expression of transcription factor FOXM1 in common malignant solid tumors in children and the molecular mechanism that promotes tumorigenesis and development.Method 1.Use databases such as GEO,TARGET,GTEx and Array Express to screen human hepatoblastoma(HB),Wilms’ tumor(WT)and neuroblastoma(NB)that meet the set conditions Tissue microarray and RNA sequencing(RNA-seq)data to calculate the expression of FOXM1 in three tumors.2.Collect fresh tissues from patients with HB and Wilms tumor in our hospital for high-throughput sequencing to detect FOXM1 expression levels.Because this study did not collect paracancerous tissues from patients with neuroblastoma,there is no neuroblastoma in this study.RNA-seq data.3.In order to further evaluate the expression of the transcription factor FOXM1 in the three tumors,this study used a meta-analysis to further verify its expression level.4.It was reported that FOXM1 is up-regulated in HB,but the specific mechanism is unknown.In order to study its molecular mechanism,this study took the human hepatoblastoma hep G2 cell line as the research object to explore the possible molecular mechanism of FOXM1 in hepatoblastoma.si RNA transfected human hepatoblastoma hep G2 cell line to silence the transcription factor FOXM1,RT-q PCR and Western blotting were used to verify the silencing efficiency.CCK-8,plate cloning experiment,Transwell invasion experiment,scratch experiment and flow cytometry were used to analyze FOXM1 The effect of human hepatoblastoma Hep G2 cell proliferation,migration,cell cycle and apoptosis.Results 1.Filtering by database qualifications,HB,WT,and NB screened out 10,4,and 3 eligible chips and data sets,respectively.2.The RNA-seq results of three internal HB children showed that the difference between HB tissue and normal liver tissue was not statistically significant,but the reliability of the evaluation was also not statistically significant(t test: 3HB vs 3NL,p = 0.2810,ROC : AUC = 0.8889,p = 0.1266).In the database screening results,with the exception of GSE51701,the other microarray and RNA-seq data set results showed that the expression level of HB tissue was significantly higher than that of normal liver tissue,and its credibility was high(t test: p < 0.05,ROC: AUC > 0.75,p < 0.05).In WT,GSE11024,GSE73209 and TARGET-GTEx tumor tissue and normal kidney tissue FOXM1 expression difference analysis results showed that the expression level of WT tissue was significantly up-regulated compared with normal kidney tissue,and the reliability was high(t test: p < 0.05,ROC: AUC > 0.750.80,p < 0.05).Since the undergraduate room did not collect NB adjacent tissues,there is no RNA-seq data of NB clinical samples in this study.The t-test results indicated that the expression of transcription factor FOXM1 in E-MEXP-669 and GTEx-TARGET tumor tissues was significantly higher than that in normal tissues(p < 0.05,AUC > 0.75).3.The meta-analysis results suggest that overall SMD = 2.02,95%CI = 1.41-2.63,where HB SMD = 1.40,95%CI = 1.09-1.71,WT SMD = 3.01,95%CI = 0.61-5.41,NB SMD = 2.03,95%CI = 1.37-2.68,s ROC AUC = 0.96,indicating that the expression level of FOXM1 in hepatoblastoma tissue is significantly higher than that in normal liver tissue,and the reliability is high.In addition,internal high-throughput sequencing data showed that the expression of FOXM1 in HB tissue was significantly higher than that in normal liver tissue(p < 0.05).4.Verify the silencing efficiency of FOXM1 gene in human hepatoblastoma hep G2 cells by RT-q PCR and Western blotting.The results of CCK-8,Transwell invasion test,scratch test,and flow cytometry show that silencing FOXM1 can inhibit the migration,invasion and proliferation of human hepatoblastoma hep G2 cells,while blocking the tumor cell cycle in S phase and promoting tumor cell apoptosis.Conclusion The transcription factor FOXM1 was significantly upregulated in hepatoblastoma,nephroblastoma,and neuroblastoma tumor tissues,which can be used as a tumor marker of hepatoblastoma.The downregulation of FOXM1 can inhibit the migration,invasion and proliferation of Hep G2 cell line,block the tumor cell cycle in S phase and promote the apoptosis of tumor cells.