Deregulated microRNAs in triple-negative breast cancer revealed by deep sequencing.
Deregulated microRNAs in triple-negative breast cancer revealed by deep sequencing.
复制标题
DOI：
10.1186/s12943-015-0301-9
复制
发表时间：
2015-02-10
期刊：
影响因子：
37.3
通讯作者：
Chuang EY
中科院分区：
文献类型：
--
作者：
Chang YY;Kuo WH;Hung JH;Lee CY;Lee YH;Chang YC;Lin WC;Shen CY;Huang CS;Hsieh FJ;Lai LC;Tsai MH;Chang KJ;Chuang EY
microRNA（miRNAs）是一种短的非编码RNA分子，在人类恶性肿瘤中起关键作用。然而，三阴性乳腺癌（一种不表达雌激素受体、孕激素受体和人表皮生长因子受体2基因的乳腺癌表型）中miRNA的调节特征仍然知之甚少。在这项研究中，使用深度测序技术分析了24例三阴性乳腺癌和14例癌旁正常组织的miRNA表达谱。使用分位数-分位数缩放方法对miRNA读数的表达水平进行标准化。使用Student t检验从测序数据中鉴定三阴性乳腺癌中失调的miRNA。进行定量逆转录PCR验证以检查miRNA表达水平。使用已发表的靶标预测算法预测miRNA的潜在靶标候选物。进行荧光素酶报告基因测定实验以验证推定的miRNA-靶标关系。从策展的数据库中检索了失调的miRNA的验证分子靶点，并讨论了它们与癌症进展的相关性。在分层聚类分析中，发现一种新的25-miRNA表达特征可以有效区分三阴性乳腺癌和周围正常组织。我们记录了七个多顺反子miRNA簇在三阴性乳腺癌中优先携带失调的miRNA的证据。其中两个小RNA簇在三阴性乳腺癌中，5 q32的miR-143-145和17p13.1的miR-497-195显著下调，而其他5个miRNA簇在三阴性乳腺癌中显著下调。三阴性乳腺癌中miR-17-92（13q31.3）、miR-183-182（7q32.2）、miR-200-429（1p36.33）、miR-301 b-130 b（22q11.21）和miR-532-502（Xp11.23）表达上调。此外，来自miR-301 b-130 b簇的miR-130 b-5 p显示直接抑制三阴性乳腺癌细胞中的细胞周期蛋白G2（CCNG 2）基因，这是一种关键的细胞周期调节因子。荧光素酶报告基因分析表明，miR-130 b-5 p介导的CCNG 2抑制作用依赖于3′-非翻译区序列。这项研究中描述的发现暗示miR-130 b-5 p-CCNG 2轴可能参与三阴性乳腺癌的恶性进展。我们的工作提供了一个清晰的图片在三阴性乳腺癌的全球miRNA调控特征，并扩展了目前的microRNA调控网络的知识。本文的在线版本（doi：10.1186/s12943-015-0301-9）包含补充材料，可供授权用户使用。
MicroRNAs (miRNAs) are short, non-coding RNA molecules that play critical roles in human malignancy. However, the regulatory characteristics of miRNAs in triple-negative breast cancer, a phenotype of breast cancer that does not express the genes for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, are still poorly understood. In this study, miRNA expression profiles of 24 triple-negative breast cancers and 14 adjacent normal tissues were analyzed using deep sequencing technology. Expression levels of miRNA reads were normalized with the quantile-quantile scaling method. Deregulated miRNAs in triple-negative breast cancer were identified from the sequencing data using the Student’s t-test. Quantitative reverse transcription PCR validations were carried out to examine miRNA expression levels. Potential target candidates of a miRNA were predicted using published target prediction algorithms. Luciferase reporter assay experiments were performed to verify a putative miRNA-target relationship. Validated molecular targets of the deregulated miRNAs were retrieved from curated databases and their associations with cancer progression were discussed. A novel 25-miRNA expression signature was found to effectively distinguish triple-negative breast cancers from surrounding normal tissues in a hierarchical clustering analysis. We documented the evidence of seven polycistronic miRNA clusters preferentially harboring deregulated miRNAs in triple-negative breast cancer. Two of these miRNA clusters (miR-143-145 at 5q32 and miR-497-195 at 17p13.1) were markedly down-regulated in triple-negative breast cancer, while the other five miRNA clusters (miR-17-92 at 13q31.3, miR-183-182 at 7q32.2, miR-200-429 at 1p36.33, miR-301b-130b at 22q11.21, and miR-532-502 at Xp11.23) were up-regulated in triple-negative breast cancer. Moreover, miR-130b-5p from the miR-301b-130b cluster was shown to directly repress the cyclin G2 (CCNG2) gene, a crucial cell cycle regulator, in triple-negative breast cancer cells. Luciferase reporter assays showed that miR-130b-5p-mediated repression of CCNG2 was dependent on the sequence of the 3′-untranslated region. The findings described in this study implicate a miR-130b-5p-CCNG2 axis that may be involved in the malignant progression of triple-negative breast cancer. Our work delivers a clear picture of the global miRNA regulatory characteristics in triple-negative breast cancer and extends the current knowledge of microRNA regulatory network. The online version of this article (doi:10.1186/s12943-015-0301-9) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
3.7
作者：
Lu TP;Lee CY;Tsai MH;Chiu YC;Hsiao CK;Lai LC;Chuang EY
通讯作者：
Chuang EY
皮肤黑色素瘤中 RUNX3 抑癌基因表达的调节。
DOI：
10.1158/1078-0432.ccr-08-3172
发表时间：
2009-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kitago M;Martinez SR;Nakamura T;Sim MS;Hoon DS
通讯作者：
Hoon DS
DOI：
10.1073/pnas.0808042106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Sachdeva, Mohit;Zhu, Shoumin;Mo, Yin-Yuan
通讯作者：
Mo, Yin-Yuan
影响因子：
4.8
作者：
Horne, MC;Donaldson, KL;Wahl, AF
通讯作者：
Wahl, AF
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C