Oncogenic long noncoding RNA landscape in breast cancer.
Oncogenic long noncoding RNA landscape in breast cancer.
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乳腺癌中的致癌长链非编码 RNA 景观。
DOI：
10.1186/s12943-017-0696-6
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发表时间：
2017-07-24
期刊：
影响因子：
37.3
通讯作者：
Pang D
中科院分区：
文献类型：
--
作者：
Xu S;Kong D;Chen Q;Ping Y;Pang D
很少有长链非编码RNA（lncRNA）在乳腺癌中作为致癌基因被发现。与肿瘤发生和更差的生存结果相关的致癌lncRNA分别在基因表达Omnibus（GEO）和癌症基因组图谱（TCGA）中进行了检查和验证。通过生物信息学和基因组数据分析，研究了这些lncRNA的潜在生物学功能和表达调控。此外，在我们的队列中通过高通量测序和TCGA验证研究了进行性乳腺癌亚型特异性lncRNA。为了阐明这些lncRNA的调节机制，然后应用并检查来自TCGA、Broad、桑格和BCCRC数据的基因组改变以及来自GEO数据的表观遗传修饰以满足该目标。最后，应用细胞增殖测定、流式细胞术分析和TUNEL测定来验证这些lncRNA在体外的致癌作用。一组致癌lncRNA在乳腺癌组织中上调，并与较差的生存结果相关。这些致癌lncRNA参与调节免疫系统激活以及TGF-β和Jak-STAT信号通路。此外，TINCR、LINC 00511和PPP 1 R26-AS 1分别被鉴定为与HER-2、三阴性和管腔型B乳腺癌亚型相关的亚型特异性lncRNA。这些致癌lncRNA的上调主要由乳腺癌和其他实体瘤中基因组中的基因扩增引起。最后，TINCR、DSCAM-AS 1或HOTAIR的敲低在体外抑制乳腺癌细胞增殖，增加凋亡并抑制细胞周期进展。这些发现增强了乳腺癌中已知致癌lncRNA的景观，并提供了对其作用的见解。这种理解可能有助于乳腺癌的综合治疗。本文的在线版本（doi：10.1186/s12943-017-0696-6）包含补充材料，可供授权用户使用。
Few long noncoding RNAs (lncRNAs) that act as oncogenic genes in breast cancer have been identified. Oncogenic lncRNAs associated with tumourigenesis and worse survival outcomes were examined and validated in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), respectively. Then, the potential biological functions and expression regulation of these lncRNAs were studied via bioinformatics and genome data analysis. Moreover, progressive breast cancer subtype-specific lncRNAs were investigated via high-throughput sequencing in our cohort and TCGA validation. To elucidate the mechanisms of the regulation of these lncRNAs, genomic alterations from the TCGA, Broad, Sanger and BCCRC data, as well as epigenetic modifications from GEO data, were then applied and examined to meet this objective. Finally, cell proliferation assays, flow cytometry analyses and TUNEL assays were applied to validate the oncogenic roles of these lncRNAs in vitro. A cluster of oncogenic lncRNAs that was upregulated in breast cancer tissue and was associated with worse survival outcomes was identified. These oncogenic lncRNAs are involved in regulating immune system activation and the TGF-beta and Jak-STAT signalling pathways. Moreover, TINCR, LINC00511, and PPP1R26-AS1 were identified as subtype-specific lncRNAs associated with HER-2, triple-negative and luminal B subtypes of breast cancer, respectively. The up-regulation of these oncogenic lncRNAs is mainly caused by gene amplification in the genome in breast cancer and other solid tumours. Finally, the knockdown of TINCR, DSCAM-AS1 or HOTAIR inhibited breast cancer cell proliferation, increased apoptosis and inhibited cell cycle progression in vitro. These findings enhance the landscape of known oncogenic lncRNAs in breast cancer and provide insights into their roles. This understanding may potentially aid in the comprehensive management of breast cancer. The online version of this article (doi:10.1186/s12943-017-0696-6) contains supplementary material, which is available to authorized users.
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