Bromodomain Proteins Epigenetically Regulate the Mitotically Associated lncRNA MANCR in Triple Negative Breast Cancer Cells.

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Kirsten M Tracy, Shannon Prior, Willem T Trowbridge, Joseph R Boyd, Prachi N Ghule, Seth Frietze, Janet L Stein, Gary S Stein, Jane B Lian
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引用次数: 0

Abstract

Long non-coding RNA (lncRNA)-mediated control of gene expression contributes to regulation of biological processes that include proliferation and phenotype, as well as compromised expression of genes that are functionally linked to cancer initiation and tumor progression. lncRNAs have emerged as novel targets and biomarkers in breast cancer. We have shown that mitotically associated lncRNA MANCR is expressed in triple-negative breast cancer (TNBC) cells and that it serves a critical role in promoting genome stability and survival in aggressive breast cancer cells. Using an siRNA strategy, we selectively depleted BRD2, BRD3, and BRD4, singly and in combination, to establish which bromodomain proteins regulate MANCR expression in TNBC cells. Our findings were confirmed by using in situ hybridization combined with immunofluorescence analysis that revealed BRD4, either alone or with BRD2 and BRD3, can support MANCR regulation of TNBC cells. Here we provide evidence for MANCR-responsive epigenetic control of super enhancers by histone modifications that are required for gene transcription to support cell survival and expression of the epithelial tumor phenotype in triple negative breast cancer cells.

Bromodomain蛋白对三阴性乳腺癌细胞中与有丝分裂相关的lncRNA MANCR进行表观遗传调控
长非编码 RNA(lncRNA)介导的基因表达控制有助于调节生物过程,包括增殖和表型,以及与癌症发生和肿瘤进展有功能关联的基因的表达。我们的研究表明,与有丝分裂相关的 lncRNA MANCR 在三阴性乳腺癌(TNBC)细胞中表达,它在促进侵袭性乳腺癌细胞的基因组稳定性和存活方面发挥着关键作用。我们采用 siRNA 策略,选择性地单独或联合去除 BRD2、BRD3 和 BRD4,以确定哪些溴域蛋白调控 TNBC 细胞中 MANCR 的表达。原位杂交结合免疫荧光分析证实了我们的发现,该分析表明,BRD4单独或与BRD2和BRD3一起可支持TNBC细胞的MANCR调控。在此,我们提供了通过组蛋白修饰对超级增强子进行 MANCR 响应性表观遗传控制的证据,这些修饰是基因转录所必需的,以支持三阴性乳腺癌细胞的细胞存活和上皮肿瘤表型的表达。
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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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