非小细胞肺癌中SRSF家族蛋白的表达和预后及功能分析OA

Background and objective Non-small cell lung cancer(NSCLC)is one of the leading causes of cancer-related deaths worldwide,and its occurrence and development are closely related to complex molecular mechanisms.Alternative splicing of precursor mRNA is a key step in gene expression regulation,and its dysregulation is common in tumors.The serine/arginine-rich splicing factor(SRSF)family,a core protein family in splicing regulation,has been confirmed to play oncogenic roles in various cancers.However,systematic research on the SRSF family in NSCLC remains insufficient.This study aims to systematically analyze the specific expression patterns,clinical prognostic value,collaborative mechanisms and potential biological functions of SRSF individual members in NSCLC by the combination of bioinformatics analysis and ex-perimental verification.Methods This study integrated NSCLC transcriptome data and clinical information from public data-bases such as The Cancer Genome Atlas(TCGA)and the Cancer Cell Line Encyclopedia(CCLE),and systematically analyzed the differential expressions of SRSF family members.Kaplan-Meier survival analysis was performed to assess the correlation between the expression levels of each SRSF member and patients'overall survival(OS).Furthermore,co-expression network analysis and Gene Ontology(GO)/Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were employed to explore the biological processes and signaling pathways potentially involved by the SRSF family.Moreover,the ex-pression and function of key members were verified by reverse transcription quantitative polymerase chain reaction(RT-qPCR),cell counting kit-8(CCK-8)and cell proliferation experiments in clinical samples and cell lines.Results Multiple members of the SRSF family(e.g.,SRSF1,SRSF2,SRSF3,SRSF6,SRSF7,SRSF9,SRSF10)were found to be significantly upregulated in NSCLC tissues and cell lines.Survival analysis indicated that high expression of SRSF9 was associated with poor prognosis,while low expressions of SRSF11 and SRSF12 also indicated unfavorable outcomes.Functional enrichment analysis revealed that the SRSF family is not only involved in RNA splicing but also significantly enriched in pathways related to protein ho-meostasis,cellular stress response,and neurodegenerative diseases.In vitro experiments confirmed that knockdown of SRSF1,SRSF2,SRSF6,SRSF9 and SRSF10 significantly inhibited the proliferation of NSCLC cells.Conclusion This study systemati-cally delineates the expression and functional landscape of the SRSF family in NSCLC,confirming their potential as prognostic biomarkers and therapeutic targets.The findings suggest that the SRSF family may drive NSCLC progression by disrupting cellular homeostasis,a crucial aspect of tumorigenesis,such as protein homeostasis and stress responses.This research provides a theoretical foundation for a deeper understanding of the role of splicing dysregulation in lung cancer and for the development of novel therapeutic strategies.