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新型 lncRNAs 共表达网络鉴定 LINC00504 在腔 A 型乳腺癌细胞中的致癌作用。

Novel lncRNAs Co-Expression Networks Identifies LINC00504 with Oncogenic Role in Luminal A Breast Cancer Cells.

机构信息

Post-Graduation Program in Genetics, Department of Genetics, Federal University of Parana, Curitiba 81530-900, PR, Brazil.

Cartes d'Identité des Tumeurs Program, Ligue Nationale Contre le Cancer, 75013 Paris, France.

出版信息

Int J Mol Sci. 2021 Feb 28;22(5):2420. doi: 10.3390/ijms22052420.

Abstract

Long non-coding RNAs (lncRNAs) are functional transcripts with more than 200 nucleotides. These molecules exhibit great regulatory capacity and may act at different levels of gene expression regulation. Despite this regulatory versatility, the biology of these molecules is still poorly understood. Computational approaches are being increasingly used to elucidate biological mechanisms in which these lncRNAs may be involved. Co-expression networks can serve as great allies in elucidating the possible regulatory contexts in which these molecules are involved. Herein, we propose the use of the pipeline deposited in the RTN package to build lncRNAs co-expression networks using TCGA breast cancer (BC) cohort data. Worldwide, BC is the most common cancer in women and has great molecular heterogeneity. We identified an enriched co-expression network for the validation of relevant cell processes in the context of BC, including LINC00504. This lncRNA has increased expression in luminal subtype A samples, and is associated with prognosis in basal-like subtype. Silencing this lncRNA in luminal A cell lines resulted in decreased cell viability and colony formation. These results highlight the relevance of the proposed method for the identification of lncRNAs in specific biological contexts.

摘要

长链非编码 RNA(lncRNAs)是具有超过 200 个核苷酸的功能性转录本。这些分子表现出很强的调节能力,可能在基因表达调控的不同水平上发挥作用。尽管具有这种调节的多功能性,但这些分子的生物学功能仍知之甚少。计算方法正越来越多地被用于阐明这些 lncRNAs 可能参与的生物学机制。共表达网络可以作为阐明这些分子可能参与的可能调节背景的重要盟友。在此,我们提出使用 RTN 软件包中提交的管道,使用 TCGA 乳腺癌(BC)队列数据构建 lncRNAs 共表达网络。在全球范围内,BC 是女性中最常见的癌症,具有很大的分子异质性。我们确定了一个富集的共表达网络,用于验证 BC 背景下相关的细胞过程,包括 LINC00504。这种 lncRNA 在腔面亚型 A 样本中表达增加,与基底样亚型的预后相关。沉默腔面 A 细胞系中的这种 lncRNA 会导致细胞活力和集落形成减少。这些结果突出了所提出的方法在特定生物背景下识别 lncRNAs 的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c35/7957645/b2bd395b209b/ijms-22-02420-g001.jpg

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