首页|期刊导航|生命科学研究|基于生物信息学分析RNA结合蛋白SAMD4家族在乳腺癌中的表达和功能差异

基于生物信息学分析RNA结合蛋白SAMD4家族在乳腺癌中的表达和功能差异OA

Bioinformatics-based Analysis of Expression and Functional Differences of the RNA-binding Protein SAMD4 Family in Breast Cancer

中文摘要英文摘要

SAMD4(sterile alpha motif domain-containing protein 4)家族是一类进化上高度保守的RNA结合蛋白,包含SAMD4A和SAMD4B两个成员,其核心功能与RNA代谢调控相关,而二者的表达异常可能参与肿瘤的发生发展过程.近期研究显示,SAMD4A在乳腺癌中表达下降并发挥抑癌作用,但SAMD4B在乳腺癌中的功能尚未明确.基于此,本研究采用生物信息学方法系统分析SAMD4A与SAMD4B在乳腺癌中的表达及功能差异.多数据库整合分析显示,虽然SAMD4A和SAMD4B的蛋白质序列高度同源且结构域相似,但二者在乳腺癌中的表达模式截然相反:SAMD4A在乳腺癌组织中呈低表达,且其低表达与患者不良预后相关;SAMD4B则在乳腺癌组织中高表达,提示二者可能具有不同的功能属性.进一步分析显示,乳腺癌组织中SAMD4A的甲基化水平显著高于正常组织,而SAMD4B的甲基化水平呈相反趋势.此外,通过对与SAMD4A、SAMD4B共表达的40个基因进行GO功能、KEGG通路富集及蛋白质互作网络分析,筛选出二者调控乳腺癌发生发展的3个关键基因PDGFRA、COX7C和BRD4;同时,还分别鉴定出与乳腺癌进展相关的调控SAMD4A和SAMD4B表达的各2个上游微RNA(microRNA,miRNA).上述结果表明,RNA结合蛋白SAMD4家族在乳腺癌中的表达和功能存在明显差异,提示它们可能作为乳腺癌临床诊断与预后评估的重要分子标志物.

Sterile alpha motif domain-containing protein 4(SAMD4)family is a group of evolutionarily highly conserved RNA-binding proteins,consisting of two members,SAMD4A and SAMD4B.Their core functions are associated with the regulation of RNA metabolism,while aberrant expression of both proteins may be in-volved in the occurrence and development of tumors.Recent studies have demonstrated that SAMD4A is down-regulated in breast cancer and exerts tumor-suppressive effects,but the function of SAMD4B in this disease remains unclear.This study systematically analyzed differences in expression and function between SAMD4A and SAMD4B in breast cancer using bioinformatics methods.Through integrated analysis of multiple data-bases,it was found that although SAMD4A and SAMD4B have highly homologous protein sequences and similar structural domains,their expression patterns in breast cancer are completely opposite:SAMD4A was downregulated in breast cancer tissues,and its low expression was associated with poor prognosis of patients,while SAMD4B was upregulated in breast cancer tissues,suggesting that the two proteins may have different functional properties.Further analysis showed that the methylation level of SAMD4A was significantly higher in breast cancer tissues than that in normal tissues,whereas SAMD4B methylation showed an opposite trend.In addition,through GO function,KEGG pathway enrichment and protein-protein interaction(PPI)network analyses of 40 genes co-expressed with SAMD4A and SAMD4B,three key genes(PDGFRA,COX7C and BRD4)regulated by the two proteins were identified as potentially involved in the regulation of breast cancer occurrence and development.Meanwhile,two upstream microRNAs(miRNAs)responsible for regulating the expression of SAMD4A and SAMD4B,respectively,and associated with breast cancer progression were also identified.Collectively,these results indicate that the RNA-binding proteins of the SAMD4 family exhibit distinct expression patterns and functions in breast cancer,suggesting that they may serve as important molecular markers for clinical diagnosis and prognosis of this disease.

李佳慧;王馨雅;张丽娜

北京工业大学化学与生命科学学院,中国 北京 100124北京工业大学化学与生命科学学院,中国 北京 100124北京工业大学化学与生命科学学院,中国 北京 100124

生物科学

RNA结合蛋白SAMD4ASAMD4B乳腺癌生物信息学

RNA-binding proteinSAMD4ASAMD4Bbreast cancerbioinformatics

《生命科学研究》 2026 (2)

160-171,12

国家自然科学基金面上项目(82172969)北京市自然科学基金面上项目(5202001)

10.16605/j.cnki.1007-7847.2025.06.0154

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