Study On The Role And Mechanism Of SEMA3C Missense Mutation In The Occurrence And Development Of Liver Cancer

Objective: The neural axon guidance factor Semaphorin3C(Semaphorin SEMA3C)is expressed in many tumors,but its effects on cell proliferation,invasion,and metastasis in different types of tumor cells has different results,because there is no precedent for the research of SEMA3 C mutation in the process of liver cancer,and the mechanism of abnormal expression of SEMA3 C in tumors has not been elucidated.Therefore,this study mainly discusses the mechanism of SEMA3 C mutation in the growth,invasion and metastasis of liver cancer,and analyzes the effect of the inhibitor Vandetanib on the abnormal expression of SEMA3 C.Methods: 1.Sequencing of tumor samples from 40 patients with liver cancer by exome sequencing.2.Construction of eukaryotic expression vectors of SEMA3 C wild-type WT and mutant MT.3.The migration,clone formation and proliferation abilities of the overexpression SEMA3 C wild-type and overexpression mutant rs1527482 G>A SEMA3 C on liver cancer cells were studied and the molecular mechanism was analyzed.Growth factor receptor tyrosine kinase(RTK)pathway activation is a key mechanism that mediates tumor growth,survival,and treatment resistance.Homologous ligands play a key role in autocrine or paracrine stimulation of these RTK pathways.This article demonstrates that SEMA3 C drives activation of multiple RTKs including EGFR,VEGFR2,and MET in a ligandindependent manner via plexin PLXND1 and PLXNB1.4.To study the effects of wild type and mutant type of overexpression SEMA3 C on subcutaneous tumorigenesis in nude mice,and the efficacy of EGFR inhibitor Vandetanib on subcutaneous tumorigenesis.SEMA3 C inhibition represents a novel therapeutic strategy for treatment of advanced liver cancer.Results: 1.According to the exome sequencing results of 40 patients with liver cancer,8 cases of rs1527482 G>A mutation of SEMA3 C in the 20 patients with high metastatic potential group and 1 case of rs1527482 G>A mutation of SEMA3 C in the 20 patients with low metastatic potential group were found.2.In the hepatocellular carcinoma cell lines PLC / PRF / 5 and Hu H-7,the migration ability,clone formation ability,and proliferation ability of SEMA3 C mutant(MT)are all enhanced compared with the wild type(WT)and empty vector control groups(NC),but there is no significant difference in apoptosis levels between NC,WT,and MT.3.In a nude mouse subcutaneous tumor model of the liver cancer cell line PLC / PRF / 5,the tumor mass and volume of the SEMA3 C mutant(MT)in the nonmedicated group was larger than that of the wild type(WT)and empty vector control group(NC).In the Vandetanib treatment group,the subcutaneous tumors in the three groups of NC,WT,and MT are all significantly reduced.From the point of view of reduction,MT decreased more.Conclusion: This study shows that SEMA3 C plays an important role in the occurrence and development of liver cancer.In summary,overexpression of SEMA3 C or expression of SEMA3 C with rs1527482 G> A mutation in HCC can be used as a candidate marker for the diagnosis of liver cancer.At the same time,SEMA3 C shows the characteristics and functions of oncogenic genes in liver cancer,which will lay a theoretical foundation for elucidating the relationship between abnormal SEMA3 C expression and the pathogenesis of liver cancer,and provide a new target and direction for the clinical treatment and diagnosis of liver cancer.