Selective expression of long non-coding RNAs in a breast cancer cell progression model.

Selective expression of long non-coding RNAs in a breast cancer cell progression model.
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DOI:
10.1002/jcp.25997
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发表时间:
2018-03
影响因子:
5.6
通讯作者:
Stein GS
Stein GS
中科院分区:
生物学2区
文献类型:
--
作者:
Tracy KM;Tye CE;Page NA;Fritz AJ;Stein JL;Lian JB;Stein GS

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长链非编码RNA被认为是癌症生物学和病理学的调节因子。我们的目标是对代表疾病进展的乳腺癌细胞系进行严格的分析。我们使用MCF-10系列,包括正常样MCF-10A、HRAS转化的MCF-10AT 1(癌前)和MCF-10 CA 1a(恶性)细胞,进行转录组范围测序。从这些数据中,我们已经确定了346个lncRNA在整个进展系列中表达失调。通过将来自这些数据集的lncRNA与来自代表不同疾病阶段和亚型的另外一组细胞系MCF-7(早期,管腔型)和MDA-MB-231(晚期,基底型)的那些lncRNA进行比较,鉴定了61种与乳腺癌进展相关的lncRNA。从癌症基因组图谱中查询乳腺癌患者数据,我们选择了一种具有潜在临床相关性的lncRNA IGFL 2-AS 1用于功能表征。在61种lncRNA中,IGFL 2-AS 1的降低最显著。我们的研究结果表明,这种lncRNA在下调其最近的邻居IGFL 1中发挥作用,并影响乳腺癌细胞的迁移。此外,我们鉴定的lncRNA为从机制和临床上理解lncRNA在乳腺癌进展中的作用提供了宝贵的资源。
Long non-coding RNAs are acknowledged as regulators of cancer biology and pathology. Our goal was to perform a stringent profiling of breast cancer cell lines that represent disease progression. We used the MCF-10 series, which includes the normal-like MCF-10A, HRAS-transformed MCF-10AT1 (pre-malignant), and MCF-10CA1a (malignant) cells, to perform transcriptome wide sequencing. From these data, we have identified 346 lncRNAs with dysregulated expression across the progression series. By comparing lncRNAs from these datasets to those from an additional set of cell lines that represent different disease stages and subtypes, MCF-7 (early stage, luminal), and MDA-MB-231 (late stage, basal), 61 lncRNAs that are associated with breast cancer progression were identified. Querying breast cancer patient data from The Cancer Genome Atlas, we selected a lncRNA, IGFL2-AS1, of potential clinical relevance for functional characterization. Among the 61 lncRNAs, IGFL2-AS1 was the most significantly decreased. Our results indicate that this lncRNA plays a role in downregulating its nearest neighbor, IGFL1, and affects migration of breast cancer cells. Furthermore, the lncRNAs we identified provide a valuable resource to mechanistically and clinically understand the contribution of lncRNAs in breast cancer progression.
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