Deep Sequencing of Serum Small RNAs Identifies Patterns of 5' tRNA Half and YRNA Fragment Expression Associated with Breast Cancer.
Deep Sequencing of Serum Small RNAs Identifies Patterns of 5' tRNA Half and YRNA Fragment Expression Associated with Breast Cancer.
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DOI：
10.4137/bic.s20764
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Martin DI
中科院分区：
文献类型：
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作者：
Dhahbi JM;Spindler SR;Atamna H;Boffelli D;Martin DI
血液中循环的小的非编码RNA可以作为信号分子，因为它们有能力执行各种细胞功能。我们以前曾将tRNA和YRNA衍生的小RNA描述为人类和小鼠血液中较大复合体的组成部分；这些小RNA的特征意味着特定的加工、分泌和生理调节。在这项研究中，我们询问了这些tRNA和YRNA片段血清丰度的变化是否与癌症的诊断有关。我们使用深度测序和信息学分析对乳腺癌患者和正常对照血清中的小RNA进行分类。在两组中都有丰富的5‘tRNA片段和YRNA片段，但我们发现乳腺癌的诊断与特定亚型水平的变化有关。这促使我们查看了42例乳腺癌患者在诊断时采集的血清小RNA的现有序列数据集。我们发现与癌症的临床病理特征相关的特异性5‘tRNA片段和YRNA片段的水平发生了显著变化。尽管这些发现没有建立因果关系，但它们表明循环中具有已知细胞功能的5‘tRNA片段和YRNA片段可能参与乳腺癌综合征，并有可能作为循环生物标记物。需要对多种癌症进行更大规模的研究，以充分评估它们在发展非侵入性癌症筛查方面的潜在用途。
Small noncoding RNAs circulating in the blood may serve as signaling molecules because of their ability to carry out a variety of cellular functions. We have previously described tRNA- and YRNA-derived small RNAs circulating as components of larger complexes in the blood of humans and mice; the characteristics of these small RNAs imply specific processing, secretion, and physiological regulation. In this study, we have asked if changes in the serum abundance of these tRNA and YRNA fragments are associated with a diagnosis of cancer. We used deep sequencing and informatics analysis to catalog small RNAs in the sera of breast cancer cases and normal controls. 5′ tRNA halves and YRNA fragments are abundant in both groups, but we found that a breast cancer diagnosis is associated with changes in levels of specific subtypes. This prompted us to look at existing sequence datasets of serum small RNAs from 42 breast cancer cases, taken at the time of diagnosis. We find significant changes in the levels of specific 5′ tRNA halves and YRNA fragments associated with clinicopathologic characteristics of the cancer. Although these findings do not establish causality, they suggest that circulating 5′ tRNA halves and YRNA fragments with known cellular functions may participate in breast cancer syndromes and have potential as circulating biomarkers. Larger studies with multiple types of cancer are needed to adequately evaluate their potential use for the development of noninvasive cancer screening.