Role of lncRNA BC030870 in mammary gland cell proliferation

We investigated an uncharacterized lncRNA, BC030870, that displays an epithelial cell-restricted expression, is downregulated by TGF-β in mammary gland cells, and controls —among others— Cdkn1a (p21WAF1/Cip1) gene expression at both transcriptional and post-transcriptional levels. BC030870 encodes a functionally active microptide (EPRp) that interacts with proteins belonging to apical junctional complexes. We hypothesized that: 1. BC030870 operates at multiple levels to orchestrate gene networks able to control cell fate, proliferation, and adhesion/migration in epithelial mammary gland cells and 2. the reduced expression of BC030870 in a group of breast cancer cells plays a role in tumor growth and invasiveness. Thus, we wanted to define the transcriptomic changes induced by BC030870 over-expression and to verify the contribution of the EPRp to gene expression changes. Comparison of the transcriptome changes caused by stable over-expression of either lncRNA BC030870 or a point mutant version unable to generate a small peptide.本研究针对未被表征的长链非编码RNA（long non-coding RNA，lncRNA）BC030870展开探究：该RNA呈现上皮细胞限制性表达模式，可在乳腺细胞中被转化生长因子β（transforming growth factor-β，TGF-β）下调，并可在转录及转录后水平调控包括细胞周期蛋白依赖性激酶抑制剂1A（Cdkn1a, p21WAF1/Cip1）在内的多种基因的表达。BC030870可编码具有功能活性的微肽（EPRp），该微肽可与顶端连接复合体相关蛋白发生相互作用。本研究提出如下两项假说：其一，BC030870可通过多层面机制调控基因网络，进而掌控上皮乳腺细胞的细胞命运、增殖以及黏附与迁移过程；其二，部分乳腺癌细胞中BC030870的表达下调可参与肿瘤生长与侵袭进程。据此，本研究旨在明确BC030870过表达所诱导的转录组变化，并验证EPRp对基因表达调控的贡献。具体而言，我们将比较分别稳定过表达lncRNA BC030870与无法产生小肽的点突变体所引发的转录组差异。