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三阴性乳腺癌中失调的长链非编码RNA的微阵列表达谱分析。

Microarray expression profiling of dysregulated long non-coding RNAs in triple-negative breast cancer.

作者信息

Chen Chen, Li Zhilu, Yang Yuan, Xiang Tingxiu, Song Weihong, Liu Shengchun

机构信息

a Department of Surgery ; The First Affiliated Hospital of Chongqing Medical University ; Chongqing , China.

出版信息

Cancer Biol Ther. 2015;16(6):856-65. doi: 10.1080/15384047.2015.1040957.

Abstract

Triple-negative breast cancer (TNBC) represents a collection of malignant breast tumors that are often aggressive and have an increased risk of metastasis and relapse. Long non-coding RNAs are generally defined as RNA transcripts measuring 200 nucleotides or longer that do not encode for any protein. During the past decade, increasing evidence has shown that lncRNAs play important roles in oncogenesis and tumor suppression; however, the roles of lncRNAs in TNBC are poorly understood. To address this issue, we used Agilent human lncRNA microarray chips and bioinformatics tools, including Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), to assess lncRNA expression in 3 pairs of TNBC tissues. A dysregulated lncRNA expression profile was identified by microarray and verified by qRT-PCR in 48 pairs of breast cancer subtype tissues. Metastasis is the major cause of cancer-related deaths, including those in TNBC, and the presence of dormant residual disseminated tumor cells (DTC) may be a key factor leading to metastasis. ANKRD30A, a potential target for breast cancer immunotherapy, is currently one of the most used DTC markers. Notably, we found the expression levels of the novel intergenic lncRNA LINC00993 to be associated with the expression levels of ANKRD30A. Furthermore, our qRT-PCR data indicated that the expression of LINC00993 was also associated with the expression of the estrogen receptor. In conclusion, our study identified a set of lncRNAs that were consistently aberrantly expressed in TNBC, and these dysregulated lncRNAs may be involved in the development and/or progression of TNBC.

摘要

三阴性乳腺癌(TNBC)是一类恶性乳腺肿瘤,通常侵袭性强,转移和复发风险增加。长链非编码RNA一般被定义为长度为200个核苷酸或更长且不编码任何蛋白质的RNA转录本。在过去十年中,越来越多的证据表明长链非编码RNA在肿瘤发生和肿瘤抑制中发挥重要作用;然而,长链非编码RNA在三阴性乳腺癌中的作用仍知之甚少。为了解决这个问题,我们使用安捷伦人类长链非编码RNA微阵列芯片和生物信息学工具,包括基因本体论(GO)和京都基因与基因组百科全书(KEGG),来评估3对三阴性乳腺癌组织中的长链非编码RNA表达。通过微阵列鉴定出失调的长链非编码RNA表达谱,并在48对乳腺癌亚型组织中通过qRT-PCR进行验证。转移是癌症相关死亡的主要原因,包括三阴性乳腺癌患者的死亡,而休眠残留播散肿瘤细胞(DTC)的存在可能是导致转移的关键因素。ANKRD30A是乳腺癌免疫治疗的一个潜在靶点,目前是最常用的DTC标志物之一。值得注意的是,我们发现新型基因间长链非编码RNA LINC00993的表达水平与ANKRD30A的表达水平相关。此外,我们的qRT-PCR数据表明LINC00993的表达也与雌激素受体的表达相关。总之,我们的研究鉴定出一组在三阴性乳腺癌中持续异常表达的长链非编码RNA,这些失调的长链非编码RNA可能参与了三阴性乳腺癌的发生和/或进展。

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