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缺氧反应性长非编码 RNA 可能影响乳腺癌的肿瘤生物学和后续管理。

The hypoxia-responsive long non-coding RNAs may impact on the tumor biology and subsequent management of breast cancer.

机构信息

Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.

Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia; Department of Medical Biology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.

出版信息

Biomed Pharmacother. 2018 Mar;99:51-58. doi: 10.1016/j.biopha.2017.12.104. Epub 2018 Jan 8.

Abstract

Long non-coding RNAs (lncRNAs) are DNA transcripts longer than 200 nucleotides without protein-coding potential. As they are key regulators of gene expression at chromatic, transcriptional and posttranscriptional level, they play important role in various biological and pathological processes. Dysregulation of lncRNAs has been observed in several diseases including cancer. Breast cancer is heterogeneous disease with many molecular subtypes specific in different prognosis and treatment responses. Hypoxia, a common micro-environmental feature of rapidly growing tumour is associated with metastases, recurrences and resistance to therapy. Aberrant expression of hypoxia related lncRNAs significantly correlates with poor outcomes in cancer patients, as the lncRNAs play an important regulatory role in the breast cancer-cell survival. Thus, a better understanding of lncRNAs role in the hypoxic conditions of breast cancer is crucial for precise understanding of the tumorigenesis, disease features and poor clinical outcome, especially in highly aggressive breast cancer subtypes (HER2-positive and triple-negative types). Moreover, lncRNAs may represent tumour marker predicting prognosis and therapeutic targets improving precise and personalized therapy for better patient´s survival. In this review, we summarize the recent information on lncRNAs in breast cancer with special focus on the hypoxia-responsive lncRNAs and their potential impact on the prognosis, therapy algorithms and individual outcomes. Presented data helps in better understanding of the specific mechanisms predicting new therapeutic agents and strategies for the pharmacological intervention.

摘要

长链非编码 RNA(lncRNA)是指长度大于 200 个核苷酸但没有蛋白编码潜力的 DNA 转录本。由于它们在染色质、转录和转录后水平上是基因表达的关键调节剂,因此在各种生物学和病理过程中发挥着重要作用。lncRNA 的失调已在包括癌症在内的几种疾病中观察到。乳腺癌是一种异质性疾病,具有许多分子亚型,在不同的预后和治疗反应方面具有特异性。缺氧是肿瘤快速生长的常见微环境特征,与转移、复发和治疗耐药性有关。与缺氧相关的 lncRNA 的异常表达与癌症患者的不良预后显著相关,因为 lncRNA 在乳腺癌细胞存活中发挥着重要的调节作用。因此,更好地了解 lncRNA 在乳腺癌缺氧条件下的作用对于精确理解肿瘤发生、疾病特征和不良临床结局(尤其是高度侵袭性的乳腺癌亚型[HER2 阳性和三阴性类型])至关重要。此外,lncRNA 可能代表预测预后的肿瘤标志物和治疗靶点,改善精确的个体化治疗,以提高患者的生存率。在这篇综述中,我们总结了乳腺癌中 lncRNA 的最新信息,特别关注了缺氧反应性 lncRNA 及其对预后、治疗算法和个体结局的潜在影响。所呈现的数据有助于更好地理解预测新治疗药物和策略的具体机制,以进行药理学干预。

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