Dhahbi Joseph M, Spindler Stephen R, Atamna Hani, Boffelli Dario, Martin David Ik
Department of Biochemistry, University of California at Riverside, Riverside, CA, USA. ; Center for Genetics, Children's Hospital Oakland Research Institute, Oakland, CA, USA.
Department of Biochemistry, University of California at Riverside, Riverside, CA, USA.
Biomark Cancer. 2014 Dec 8;6:37-47. doi: 10.4137/BIC.S20764. eCollection 2014.
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.
血液中循环的小非编码RNA可能因其执行多种细胞功能的能力而作为信号分子。我们之前曾描述过，tRNA和YRNA衍生的小RNA作为较大复合物的组成部分在人类和小鼠血液中循环；这些小RNA的特征意味着特定的加工、分泌和生理调节。在本研究中，我们探究了这些tRNA和YRNA片段的血清丰度变化是否与癌症诊断相关。我们使用深度测序和信息学分析对乳腺癌病例和正常对照血清中的小RNA进行分类。5' tRNA半体和YRNA片段在两组中均丰富，但我们发现乳腺癌诊断与特定亚型水平的变化相关。这促使我们查看42例乳腺癌病例在诊断时采集的血清小RNA的现有序列数据集。我们发现特定5' tRNA半体和YRNA片段的水平与癌症的临床病理特征存在显著变化。尽管这些发现并未确立因果关系，但它们表明具有已知细胞功能的循环5' tRNA半体和YRNA片段可能参与乳腺癌综合征，并有作为循环生物标志物的潜力。需要对多种类型癌症进行更大规模的研究，以充分评估它们在无创癌症筛查开发中的潜在用途。
