全基因组范围内研究 ER 调节的长非编码 RNA 显示，AP000439.3 可能在乳腺癌中作为细胞周期的关键调节因子发挥作用。
Genome-wide study of ER-regulated lncRNAs shows AP000439.3 may function as a key regulator of cell cycle in breast cancer.
机构信息
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, P.R. China.
Cedars-Sinai Medical Center, Division of Hematology/Oncology, University of California Los Angeles School of Medicine, Los Angeles, CA, USA.
出版信息
Oncol Rep. 2017 Nov;38(5):3227-3237. doi: 10.3892/or.2017.5975. Epub 2017 Sep 20.
Estrogen receptor (ER) plays important roles in cell growth, development and tumorigenesis. Although ER-regulated genes have been extensively investigated, little is known about roles of ER-regulated lncRNAs in breast cancer. Here, we conducted genome-wide study of ER-regulated lncRNAs by using RNA-seq, ChIP-seq and TCGA data. A total of identified 114 ER-regulated lncRNAs were identified, many of them were overexpressed in ER+ breast cancer and co-expressed with some key regulators. Silencing one of most prominent lncRNA, AP000439.3, resulted in inhibition of cell cycle progression and proliferation. Further study revealed AP000439.3 can regulate expression of CCND1 through enhancing estrogen receptor induction of CCND1. This finding revealed lncRNAs may serve as important effectors of ER in regulation of gene expression and cell phenotype in breast cancer.
雌激素受体（ER）在细胞生长、发育和肿瘤发生中发挥重要作用。尽管已经广泛研究了 ER 调节的基因，但 ER 调节的 lncRNA 在乳腺癌中的作用知之甚少。在这里，我们通过使用 RNA-seq、ChIP-seq 和 TCGA 数据进行了全基因组范围内的 ER 调节 lncRNA 研究。总共鉴定出 114 个 ER 调节的 lncRNA，其中许多在 ER+乳腺癌中表达上调，并与一些关键调节剂共表达。沉默最显著的 lncRNA 之一 AP000439.3 导致细胞周期进程和增殖受到抑制。进一步的研究表明，AP000439.3 可以通过增强雌激素受体诱导 CCND1 来调节 CCND1 的表达。这一发现揭示了 lncRNA 可能作为 ER 在乳腺癌中调节基因表达和细胞表型的重要效应子。
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