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长非编码 RNA 与前列腺癌发生:缺失的“连接”?

Long noncoding RNAs and prostate carcinogenesis: the missing 'linc'?

机构信息

Prostate Molecular Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland; Department of Urology, St. James's Hospital, Dublin, Ireland.

Prostate Molecular Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.

出版信息

Trends Mol Med. 2014 Aug;20(8):428-36. doi: 10.1016/j.molmed.2014.03.005. Epub 2014 May 13.

Abstract

Long noncoding RNAs (lncRNAs) are rapidly becoming essential pieces in the cancer puzzle. Our understanding of their functional capabilities is in its infancy. One certain fact, however, is that their molecular interactions extend beyond chromatin complexes into diverse biological processes. In prostate cancer, aberrant expression of lncRNAs is associated with disease progression. Overexpression of oncogenic lncRNAs promotes tumor-cell proliferation and metastasis through chromatin looping and distal engagement with the androgen receptor, antisense gene regulation, alternative splicing, and impeding DNA repair. Several lncRNAs, such as prostate cancer antigen 3 (PCA3), prostate cancer gene expression marker 1 (PCGEM1), and prostate cancer associated ncRNA transcript 1 (PCAT1), are highly prostate-specific, posing as attractive biomarkers. Herein we review the mechanisms of action of lncRNAs in prostate carcinogenesis and their potential clinical utility for disease.

摘要

长链非编码 RNA(lncRNA)迅速成为癌症研究中的重要组成部分。然而,我们对其功能的理解还处于起步阶段。有一点是肯定的,它们的分子相互作用不仅局限于染色质复合物,还延伸到各种生物学过程中。在前列腺癌中,lncRNA 的异常表达与疾病进展有关。致癌 lncRNA 的过表达通过染色质环化和与雄激素受体的远程结合、反义基因调控、选择性剪接以及阻碍 DNA 修复来促进肿瘤细胞的增殖和转移。一些 lncRNA,如前列腺癌抗原 3(PCA3)、前列腺癌基因表达标记 1(PCGEM1)和前列腺癌相关 ncRNA 转录本 1(PCAT1),具有高度的前列腺特异性,可作为有吸引力的生物标志物。本文综述了 lncRNA 在前列腺癌发生中的作用机制及其在疾病中的潜在临床应用价值。

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