The Splicing Factor SRSF2 Affects The Malignant Proliferation Of Human Breast Cancer By Regulating The Alternative Spling Of PLOD2

Alternative splicing of Pre-mRNA is one of the vital reasons for the diversity of human proteins.It is of great significance to life processes of organisms.Aberrant alternative splicing exists in many diseases,including cancer,and plays important roles in the development.As one member of the serine/arginine rich protein SR protein family,SRSF2 can not only regulate the alternative splicing of target genes through binding with their pre-mRNA,but also regulate gene transcription by binding with promotor sequence in DNA.In this study,the result of knocking down members of the common splicing protein family in human breast cancer cells showed that all SRSF1,SRSF2,and hnRNPM all promoted breast cancer cell proliferation.The statistical analysis of Kaplan-Meier Plotter database showed that all of them were overexpressed in human breast cancer tissues with unfavorable survival rate and poor prognosis of patients,indicating that there was a significant correlation between their expression levels and the prognosis of patients.Subsequently,the construction of a stable knockdown cell line and the experiments on tumorigenic in nude mice confirmed that both of SRSF2 and hnRNPM promoted breast cancer tumorigenesis in vivo.The results of Transcriptome Sequencing showed that both of them regulated the alternative splicing events of many downstream target genes.As a target comodulated by both of them,the alternative splicing of PLOD2 is confirmed regulated by SRSF2 by minigene.RIP showed that PLOD2 combined with the RRM domain of SRSF2 on exon15.The two splicing isoforms produced have opposite effects on the malignant proliferation of breast cancer,which means PLOD2-S promotes the proliferation of breast cancer cells while PLOD2-L inhibits the proliferation of breast cancer cells.When SRSF2 regulates the alternative splicing of downstream target genes,it tends to combine the specific RNA sequence on specific loci to work.Conclusion:The splicing factor SRSF2 promotes the malignant proliferation process of breast cancer by regulating the alternative splicing of PLOD2.When SRSF2 regulates the alternative splicing of downstream target genes,it has a tendency of conbining with specific sequence.The two splice isoforms,PLOD2-S and PLOD2-L,play diametrically opposed roles in breast cancer malignant proliferation.