| Non-small cell lung cancer mainly includes lung adenocarcinoma and lung squamous cell carcinoma.In recent years,some progress has been made in the diagnosis and treatment of lung adenocarcinoma,but the diagnosis and treatment of lung squamous cell carcinoma is still slow.The main reason is that the molecular pathogenesis of lung squamous cell carcinoma is still unclear.At the same time,there is a lack of effective early diagnosis and targeted therapy for lung squamous cell carcinoma,which leads to the low 5-year survival rate of patients with lung squamous cell carcinoma.To this end,based on the RNA expression data of lung squamous cell carcinoma tissues and adjacent tissues in TCGA lung squamous cell carcinoma database,we selected differentially expressed m RNA,mi RNA and lnc RNA in lung squamous cell carcinoma tissues,and constructed a ce RNA network regulatory map of lnc RNA-mi RNA-m RNA for differentially expressed m RNA,mi RNA and lnc RNA in lung squamous cell carcinoma.The carcinogenic effect of PLAU gene encoding u PA in lung squamous cell carcinoma was analyzed.The main results of this paper are as follows:1.The key gene PLAU was selected based on TCGA database.This paper analyzed the expression of m RNA,mi RNA and lnc RNA from 375 samples of lung squamous cell carcinoma cancer tissues and 46 samples of adjacent non-tumorous lung tissues from TCGA database.Compared with adjacent non-tumorous lung tissues,we found 3366 common differentially expressed m RNA,79 differentially expressed mi RNA and 151 differentially expressed lnc RNA in the early,middle and late stages of lung squamous cell carcinoma,among which 34 mi RNA were up-regulated,45 mi RNA were down-regulated,68 lnc RNA were up-regulated,and 83 lnc RNA were down-regulated.Enrichment analysis of Gene Ontology revealed that differential m RNA of lung squamous cell carcinoma were enriched in many GO entries,such as “signal transduction”,“cell adhesion” and “blood coagulation”.KEGG pathway enrichment analysis showed that the most prominent signaling pathways of up-regulated genes were “cell cycle”,“metabolic pathway” and “p53 signaling pathway”,while the most prominent signaling pathways of down-regulated transcripts were “complement and coagulation cascade” and “cell adhesion molecule”.At the same time,the predicted 86 m RNA,39 mi RNA and 88 lnc RNA were constructed to obtain a ce RNA network.The prognostic characteristics of ce RNA were analyzed by Cox regression.It was found that the expression of PLAU(uPA)was negatively correlated with the survival of patients with lung squamous cell carcinoma.This result initially suggested that PLAU was a key gene in the pathogenesis of lung squamous cell carcinoma.2.The expression of PLAU was detected in lung squamous cell carcinoma cells and subcutaneous tumors of mice,and the carcinogenic effect of PLAU was analyzed.The results of immunohistochemistry showed that the expression of u PA in the subcutaneous tumor tissues of lung squamous cell carcinoma mice was higher than those in normal lung tissues of mice.The results of q PCR,Western Blot and immunofluorescence showed that the m RNA and protein expression of u PA in lung squamous cell carcinoma SK-MES-1 cells was higher than those in lung bronchial epithelial cells 16-HBE-T.After constructing the PLAU overexpression plasmid and transfecting 16-HBE-T with the PLAU overexpression plasmid,q PCR analysis showed that MMP9,CCNB1 and N-cadherin were significantly up-regulated,while E-cadherin was significantly down-regulated,indicating that the overexpression of u PA enhances the invasion and migration ability of 16-HBE-T.Scratch test and CCK-8 experiment demonstrated that the capacity of migration and proliferation of 16-HBE-T cells were increased after u PA overexpression.The PLAU lentiviral interference plasmid was constructed and transfecting SK-MES-1 with the PLAU lentiviral interference plasmid.q PCR analysis showed that the m RNA expression of MMP9,CCNB1 and N-cadherin were significantly down-regulated,while the m RNA expression of E-cadherin was significantly up-regulated,indicating that the inhibition of u PA reduced the invasion and migration ability of SK-MES-1.Scratch test and CCK-8 experiment proved that the migration and proliferation ability of SK-MES-1 were weakened after the inhibition of u PA.The results show that the key cancer-promoting effect of PLAU(u PA)in lung squamous cell carcinoma.PLAU(u PA)may be a potential molecular target of lung squamous cell carcinoma,which is of great significance for the clinical diagnosis and treatment of lung squamous cell carcinoma.To sum up,this study analyzed the RNA expression data of lung squamous cell carcinoma in TCGA database.We obtained valuable differentially expressed genes of m RNA,mi RNA and lnc RNA,and constructed a ce RNA network,which provided basic data for further research on the pathogenesis of lung squamous cell carcinoma.Cox regression analysis showed that the expression of PLAU was negatively correlated with the survival time of patients with lung squamous cell carcinoma.The expression of PLAU in lung squamous cell carcinoma SK-MES-1 was significantly higher than those in normal lung cell line 16-HBET.Overexpression of PLAU promoted the migration and proliferation of 16-HBE-T,while inhibition of PLAU expression reduced the migration and proliferation of SK-MES-1.The results suggest that PLAU(u PA)plays a key role in promoting lung squamous cell carcinoma.PLAU(u PA)may be a potential molecular target of lung squamous cell carcinoma,which is of great significance in clinical diagnosis and treatment of lung squamous cell carcinoma. |
PDF Full Text Request