Tracy Kirsten M, Tye Coralee E, Page Natalie A, Fritz Andrew J, Stein Janet L, Lian Jane B, Stein Gary S
Department of Biochemistry and University of Vermont Cancer Center, The University of Vermont Larner College of Medicine, Burlington, Vermont.
J Cell Physiol. 2018 Feb;233(2):1291-1299. doi: 10.1002/jcp.25997. Epub 2017 Jun 15.
Long non-coding RNAs (lncRNAs) 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, IGF-like family member 2 antisense RNA 1 (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.
长链非编码RNA（lncRNAs）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。我们使用了MCF-10系列，其中包括正常样的MCF-10A、HRAS转化的MCF-10AT1（癌前）和MCF-10CA1a（恶性）细胞，来进行全转录组测序。从这些数据中，我们在整个进展系列中鉴定出346个表达失调的lncRNAs。通过将这些数据集中的lncRNAs与另一组代表不同疾病阶段和亚型的细胞系（MCF-7（早期，管腔型）和MDA-MB-231（晚期，基底型））中的lncRNAs进行比较，鉴定出61个与乳腺癌进展相关的lncRNAs。查询癌症基因组图谱中的乳腺癌患者数据，我们选择了一个具有潜在临床相关性的lncRNA，即胰岛素样家族成员2反义RNA 1（IGFL2-AS1）进行功能表征。在这61个lncRNAs中，IGFL2-AS1的表达下降最为显著。我们的结果表明，这种lncRNA在下调其最近邻基因IGFL1中发挥作用，并影响乳腺癌细胞的迁移。此外，我们鉴定出的lncRNAs为从机制和临床角度理解lncRNAs在乳腺癌进展中的作用提供了宝贵的资源。
