非小细胞肺癌中SRSF家族蛋白的表达和预后及功能分析
Expression,Prognostic and Functional Analysis of SRSF Family Proteins in Non-small Cell Lung Cancer
摘要
Abstract
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.关键词
肺肿瘤/SRSF家族/生存预后/选择性剪接/生物信息学分析/细胞增殖与活力Key words
Lung neoplasms/SRSF family/Survival prognosis/Alternative splicing/Bioinformatics analysis/Cell proliferation and viability引用本文复制引用
涂姝祺,潘红丽,周雪霞,李雪冰,陈宇昊,张亚龙,陈嫱,范亚光,王逸璇,张洋,李思诺,陈军..非小细胞肺癌中SRSF家族蛋白的表达和预后及功能分析[J].中国肺癌杂志,2026,29(1):15-25,11.基金项目
本研究受国家自然科学基金项目(No.82273019,No.82472643)、天津医科大学总医院优秀青年基金项目(No.22ZYYYQ01)、天津市科技重大专项与工程公共卫生科技重大专项重点项目(No.24ZXGZSY00040)、天津市卫生健康科技基金项目(No.TJWJ2023QN063)和天津市医学重点学科建设项目(No.TJYXZDXK-3-002B,No.TJYXZDXK-3-006A-2)资助 This study was supported by the grants from National Natural Science Foundation of China(No.82273019,to Xue-bing LI （No.82273019,No.82472643）
No.82472643,to Xuexia ZHOU),the Outstanding Youth Foundation of Tianjin Medical University General Hospital(No.22ZYYYQ01,to Xuexia ZHOU),Tianjin Science and Technology Major Special Project and Engineering-public Health Science and Technology Major Special Project Key Project(No.24ZXGZSY00040,to Yaguang FAN),the Tianjin Health Sci-ence and Technology Project(No.TJWJ2023QN063,to Qiang CHEN)and the Tianjin Key Medical Discipline Construction Project(No.TJYXZDXK-3-002B,to Jun CHEN （No.22ZYYYQ01,to Xuexia ZHOU）
No.TJYXZDXK-3-006A-2,to Jun CHEN). （）
