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长链非编码RNA在癌症诊断中的前景

Perspectives of Long Non-Coding RNAs in Cancer Diagnostics.

作者信息

Reis Eduardo M, Verjovski-Almeida Sergio

机构信息

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo São Paulo, Brasil.

出版信息

Front Genet. 2012 Mar 8;3:32. doi: 10.3389/fgene.2012.00032. eCollection 2012.

Abstract

Long non-coding RNAs (lncRNAs) transcribed from intergenic and intronic regions of the human genome constitute a broad class of cellular transcripts that are under intensive investigation. While only a handful of lncRNAs have been characterized, their involvement in fundamental cellular processes that control gene expression highlights a central role in cell homeostasis. Not surprisingly, aberrant expression of regulatory lncRNAs has been increasingly documented in different types of cancer, where they can mediate both oncogenic or tumor suppressor effects. Interaction with chromatin remodeling complexes that promote silencing of specific genes or modulation of splicing factor proteins seem to be two general modes of lncRNA regulation, but it is conceivable that additional mechanisms of action are yet to be unveiled. LncRNAs show greater tissue specificity compared to protein-coding mRNAs making them attractive in the search of novel diagnostics/prognostics cancer biomarkers in body fluid samples. In fact, lncRNA prostate cancer antigen 3 can be detected in urine samples and has been shown to improve diagnosis of prostate cancer. We suggest that an unbiased screening of the presence of RNAs in easily accessible body fluids such as serum and urine might reveal novel circulating lncRNAs as potential biomarkers in many types of cancer. Annotation and functional characterization of the lncRNA complement of the cancer transcriptome will conceivably provide new venues for early diagnosis and treatment of the disease.

摘要

从人类基因组的基因间区域和内含子区域转录而来的长链非编码RNA(lncRNA)构成了一类正在深入研究的广泛的细胞转录本。虽然只有少数lncRNA得到了表征,但它们参与控制基因表达的基本细胞过程,这突出了它们在细胞稳态中的核心作用。毫不奇怪,调控性lncRNA的异常表达在不同类型的癌症中越来越多地被记录下来,在这些癌症中它们可以介导致癌或肿瘤抑制作用。与促进特定基因沉默的染色质重塑复合物相互作用或调节剪接因子蛋白似乎是lncRNA调控的两种一般模式,但可以想象还有其他作用机制有待揭示。与蛋白质编码mRNA相比,lncRNA表现出更大的组织特异性,这使得它们在寻找体液样本中新型癌症诊断/预后生物标志物方面具有吸引力。事实上,lncRNA前列腺癌抗原3可以在尿液样本中检测到,并且已被证明可以改善前列腺癌的诊断。我们建议对血清和尿液等易于获取的体液中的RNA存在情况进行无偏筛选,这可能会揭示新型循环lncRNA作为多种癌症的潜在生物标志物。癌症转录组中lncRNA互补物的注释和功能表征有望为该疾病的早期诊断和治疗提供新途径。

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