Expression Of SMYD3 In Pan-cancer And Its Relationship With Prognosis And Immune Infiltratio

Objective:SET and MYND domain-containing 3(SMYD3)protein is a lysine methyltransferase,which epigenetically modifies the chromatin by methylation of histones.Recent researches have present that SMYD3 impacts the occurrence and development of breast cancer、liver cancer and other various cancers.However,there is still lack of pancancer research on SMYD3.In this article,we aimed to investigate the expression of SMYD3 in pan-cancer and its effect on survival and tumor immune infiltration.Further,this study attempts to explain its potential mechanism at the cellular level.Methods:(1)According to the data from TCGA and GTEx databases,we analyzed the transcription level of SMYD3 in different normal and tumor tissues.(2)Using online database HPA,UALCAN,etc.,we compared the protein level of SMYD3 in normal tissues and various tumors.(3)Download the patient survival information in the TCGA database,and analyze the relationship between the expression of SMYD3 and the patient survival.(4)The estimated algorithm was used to analyze the immune infiltration score of tumor patients,and evaluate the effect of SMYD3 expression on immune checkpoint blocking therapy.(5)Smyd3 knockout B16 cell line was constructed by CRISPR-Cas9,and we investigated the effect of SMYD3 on the expression of antigen presenting gene at the cell level by qPCR and flow cytometry.Results:(1)Based on the analysis of public databases,the transcription level of SMYD3 gene in various tumor tissues was higher than that in normal tissues(P<0.05).(2)The proteome database showed that the expression of SMYD3 protein in various tumor tissues was higher than that in normal tissues.(3)The high expression of SMYD3 is a risk factor for many kinds of tumor patients(P<0.05).(4)In various tumor tissues,the expression of SMYD3 was negatively correlated with the infiltration of immune cells(P<0.05).(5)Smyd3 gene of B16 cell line was successfully knocked out,and the mRNA level of antigen presenting genes was increased after Smyd3 knockout(P<0.05),and the expression level of MHC-I on the membrane surface of Smyd3 knockout B16 cells was also increased(P<0.05).Conclusion:In this study,we found that SMYD3 was highly expressed in various tumor tissues and was a risk factor for the prognosis of patients.In addition,this study explained the reason of poor prognosis caused by the high expression of SMYD3 from the perspective of immune infiltration.The high expression of SM YD3 caused the decrease of infiltration of multiple immune cells including CD8+T cells in tumor tissues.Furthermore,at the cellular level,this study verified that knockout of SMYD3 enhanced the antigen presentation function in tumor cells and increased the expression of MHC-I molecules on the cell surface.This study provides a theoretical basis for the development of anti-tumor drugs targeting SMYD3.