新疆医科大学学报

目的 通过乳腺癌差异表达长链非编码RNA(lncRNA)的筛选，探讨其在乳腺癌发生、发展中的作用及潜在功能。方法 收集2018年9月—11月新疆医科大学附属肿瘤医院5对女性乳腺癌组织标本及其癌旁正常组织（距肿瘤大于5 cm）标本，通过RNA提取、标记和杂交、芯片实验，以差异倍数（FC）≥2倍，t检验的P值<0.05作为筛选条件，筛选出差异表达的lncRNA。对筛选的lncRNA在正常乳腺组织和乳腺癌癌组织的表达量进行聚类分析。对差异lncRNA基因本体（Gene Ontology,GO)富集和京都基因与基因组百科全书（kyoto encyclopedia of genes and genomes,KEGG）信号通路分析获得lncRNA参与的生物学途径。结果 乳腺癌组织与癌旁组织相比，乳腺癌组织中具有2倍以上的差异表达（|log2FC|>1）lncRNA共有1 150条，其中上调lncRNA 551条，下调lncRNA 599条。下调lncRNA差异最显著的为XR＿159043.1(FC=26.878,P<0.05)，上调lncRNA差异最为显著的是ENST00000427451.1(FC=11.478,P<0.05)。通过GO富集分析发现，lncRNA广泛参与了包括RNA加工、DNA剪接、基因表达、含核碱基的化合物代谢、核酸转运mRNA剪接等生物学进程。KEGG信号通路富集分析发现，lncRNA参与了PI3K-AKT、RIG-I样受体信号通路，参与了癌症中的转录失调、病毒感染、雌激素信号通路等进程，并测出差异表达lncRNA有119种靶基因。结论 本研究是乳腺癌相关的lncRNA谱的补充，研究发现了一定数量差异表达的lncRNA，并预测其功能靶向基因和途径，有望为乳腺癌的靶向治疗和预后评估提供新的参考依据。

Objective To explore the role and the potential function of breast cancer in development of breast cancer by screening long-chain non-coding RNAs of breast cancer. Methods From September to November in 2018, five pairs of female breast cancer tissue specimens and normal tissues adjacent to the cancer(more than 5 cm away from the tumor) were collected and were subjected to RNA extraction, labeling and hybridization, and chip experiments. Differentially expressed on lncRNAs and were screened with the fold difference(FC) ≥ 2 times and the P value of the t-test <0.05 as the screening conditions. Cluster analysis was performed on the expression levels of the screened lncRNAs in normal breast tissues and breast cancer tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway analysis were used to obtain the biological pathways involved in lncRNAs. Results Compared with the adjacent tissues, breast cancer tissues had 1 150 lncRNAs with more than 2 fold(|log2FC|> 1) differences. 551 lncRNAs were up-regulated and 599 were down-regulated. The most significant difference in down-regulated lncRNA was XR＿159043.1(FC=26.878, P<0.05), and the most significant difference in up-regulated lncRNA was ENST00000427451.1(FC=11.478, P<0.05). It was found, through GO enrichment, that lncRNA was widely involved various biological processes including RNA processing, DNA splicing, gene expression, nucleobase-containing compound metabolic processes, and nucleic acid transport mRNA splicing were described. Through KEGG signal pathway enrichment analysis, it was found that lncRNA participates in PI3K-AKT and RIG-I-like receptor signaling pathways, and participates in transcriptional viral infections and estrogen signaling pathways in cancer. There were 119 target genes in differentially expressed lncRNA. Conclusion This study complements breast cancer-related lncRNA profiles, discovers a certain number of differentially expressed lncRNAs, and it predicts functionally targeted genes and pathways, which are expected to provide new approach for targeted therapy and prognostic evaluation for pancreatic cancer.