利用生物信息学综合分析lncRNA GAS5在三阴性乳腺癌中的功能作用  

Comprehensive analysis of the functional role of lncRNA GAS5 in triple-negative breast cancer by bioinformatics

作　　者：黄振宜 宋佳[2] 芦梓楠 孙刚[3] Huang Zhenyi;Song Jia;Lu Zinan;Sun Gang(The Third Affiliated Teaching Hospital of Xinjiang Medical University,Affiliated Cancer Hospital,Xinjiang 830001,China;Departments of Institute for Cancer Research,the Third Affiliated Teaching Hospital of Xinjiang Medical University,Affiliated Cancer Hospital,Xinjiang 830001,China;Department of Mammary/Head and Neck Surgery,the Third Affiliated Teaching Hospital of Xinjiang Medical University,Affiliated Cancer Hospital,Xinjiang 830001,China)

机构地区：[1]新疆医科大学第三临床医学院,830001 [2]新疆医科大学附属肿瘤医院肿瘤学防治研究所,830001 [3]新疆医科大学附属肿瘤医院乳腺头颈外科,830001

出　　处：《中华内分泌外科杂志》2020年第2期119-123,共5页Chinese Journal of Endocrine Surgery

基　　金：国家自然科学基金(81360391)。

摘　　要：目的利用生物信息学管理对乳腺癌和癌旁组织进行长链非编码RNA-生长停滞特异基因5(lncRNA GAS5)差异表达分析,以探讨GAS5对三阴性乳腺癌发生发展的影响。方法用基因图谱计划(The Cancer Genome Atlas,TCGA)的乳腺癌数据分析各个乳腺癌亚型及病理分期中GAS5的表达情况。利用基因表达综合数据库(Gene Expression Omnibus,GEO)中三阴性乳腺癌数据GSE76124和GSE83937对GAS5进行相关性分析,选取相关性基因并取交集。利用所得到的正相关基因做GO功能和KEGG通路富集分析。用TCGA数据库和GEO76124数据进行GAS5的GSEA分析。选取GEO数据集GSE40525和GSE76250进行三阴性乳腺癌的差异miRNA和mRNA的筛选,通过预测,构建GAS5-miRNA-mRNA的ceRNA网络。结果GAS5在乳腺癌各亚型组织中表达均较癌旁组织低。GAS5主要参与多种代谢进程包括有机物代谢、大分子代谢、氮化合物代谢等,在通路方面主要影响真核生物中的核糖体生物发生,WNT信号通路等。通过构建GAS5在三阴性乳腺癌中ceRNA调控网络,发现GAS5最有可能通过吸附hsa-miR-650和has-miR-532-5p调控包括SLC7A2和LONRF2在内的25个基因的表达,发挥抑癌基因的作用。结论lncRNA GAS5可能在乳腺癌中起到抑癌基因的作用,可为乳腺癌的基因治疗提供新的治疗靶点。Objective To study the effect of long noncoding RNA growth arrest-specifific transcript 5(lncRNA GAS5)on the occurrence and development of triple-negative breast cancer(TNBC)by analyzing the differential expression of lncrna GAS5 in The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Methods The expression of GAS5 in each subtype and pathological stage of breast cancer was studied by the TCGA data.The correlation of GAS5 was analyzed by using TNBC data GSE76124 and GSE83937 from the GEO database of the United States.The elated genes were collected and take the intersection.The positive correlation genes were used to analyze the GO function and the enrichment of KEGG pathway.GSEA of GAS5 was analyzed with TCGA database and GEO76124 data.GSE40525 and GSE76250 were selected from GEO data set to screen different miRNA and mRNA of TNBC,and construct the ceRNA network of GAS5-mirna-mrna through prediction.Results The expression of GAS5 in breast cancer was lower than that in the adjacent tissues.GAS5 was mainly involved in various metabolic processes,including organic metabolism,macromolecular metabolism,nitrogen metabolism,etc.In terms of pathway,GAS5 mainly affected the ribosome biogenesis in eukaryotes,Wnt signaling pathway.By constructing the regulatory network of GAS5 in TNBC,we found that GAS5 was most likely to regulate the expression of 25 genes including SLC7A2 and lLONRF2 by adsorbing hsa-mir-650 and has-mir-532-5p.Conclusion lncrna GAS5 may play a role of tumor suppressor gene in breast cancer and provide a new therapeutic target for gene therapy of breast cancer.

关 键 词：长链非编码RNA 生长停滞特异性转录本5 三阴性乳腺癌 GEO数据库 TCGA数据库 ceRNA网络 

分 类 号：R655.8[医药卫生—外科学] R737.9[医药卫生—临床医学]