剪接因子SF3B6通过调控基因表达促进乳腺癌细胞侵袭和迁移并影响患者预后OA

Objective To investigate the expression characteristics,functions and potential mechanism of splicing factor 3b subunit 6(SF3B6)in breast cancer.Methods TNMplot and UALCAN databases were used to analyze the expression of SF3B6 in breast cancer,and Kaplan-Meier Plotter database was used to analyze the correlation between the expression of SF3B6 and the prognosis of breast cancer patients.Small interfering RNA(siRNA)of SF3B6 was transfected into MDA-MB-231 cells to silence SF3B6(siSF3B6);CCK-8,Transwell,and flow cytometry were used to detect the effects of interfering with SF3B6 expression on cell proliferation,migration,invasion,and apoptosis.Transcriptome and proteome data of breast cancer patients in TCGA and CPTAC database were analyzed to further explore the downstream target genes and functions regulated by SF3B6.Results According to the analysis results of TNMplot,UALCAN and Kaplan-Meier Plotter databases,the expression level of SF3B6 was significantly higher in tumor tissue of breast cancer than in adjacent tissue(P＜0.05),and the high expression of SF3B6 was positively correlated with the poor relapse-free survival of patients(P＜0.000 1).SiSF3B6 significantly inhibited the proliferation,migration,and invasion abilities of MDA-MB-231 cells(P＜0.05),and promoted cell apoptosis.The analysis results of RNA-seq data with high and low expression of SF3B6 in TCGA breast cancer showed that the abnormal expression of SF3B6 could significantly change the gene expression profile,and SF3B6 induced the upregulated expression of cytokines interaction,gastric cancer,hepatocellular carcinoma and other pathway genes,including CENPA,CCNE1,CDKN2A and CDCA3,which significantly affected the prognosis of breast cancer patients(P＜0.05).Conclusion SF3B6 is highly expressed in breast cancer and plays a role in promoting cancer.It can be used as a potential biomarker or therapeutic target for breast cancer.