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三阴性乳腺癌中差异调节的miRNA、piRNA、lncRNA和sn/snoRNA的全面NGS数据分析

A Comprehensive NGS Data Analysis of Differentially Regulated miRNAs, piRNAs, lncRNAs and sn/snoRNAs in Triple Negative Breast Cancer.

作者信息

Koduru Srinivas V, Tiwari Amit K, Leberfinger Ashley, Hazard Sprague W, Kawasawa Yuka Imamura, Mahajan Milind, Ravnic Dino J

机构信息

Division of Plastic Surgery, Department of Surgery, College of Medicine, Pennsylvania State University, 500 University Drive, Hershey, PA 17033.

Department of Pharmacology & Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo - Health Sciences Campus, 300 Arlington Ave, Toledo, OH 43614.

出版信息

J Cancer. 2017 Feb 11;8(4):578-596. doi: 10.7150/jca.17633. eCollection 2017.

DOI:10.7150/jca.17633
PMID:28367238
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5370502/
Abstract

Cancer is the second leading cause of death in the United States and is a major public health concern worldwide. Basic, clinical and epidemiological research is leading to improved cancer detection, prevention, and outcomes. Recent technological advances have allowed unbiased and comprehensive screening of genome-wide gene expression. Small non-coding RNAs (sncRNAs) have been shown to play an important role in biological processes and could serve as a diagnostic, prognostic and therapeutic biomarker for specific diseases. Recent findings have begun to reveal and enhance our understanding of the complex architecture of sncRNA expression including miRNAs, piRNAs, lncRNAs, sn/snoRNAs and their relationships with biological systems. We used publicly available small RNA sequencing data that was derived from 24 triple negative breast cancers (TNBC) and 14 adjacent normal tissue samples to remap various types of sncRNAs. We found a total of 55 miRNAs were aberrantly expressed (p<0.005) in TNBC samples (8 miRNAs upregulated; 47 downregulated) compared to adjacent normal tissues whereas the original study reported only 25 novel miRs. In this study, we used pathway analysis of differentially expressed miRNAs which revealed TGF-beta signaling pathways to be profoundly affected in the TNBC samples. Furthermore, our comprehensive re-mapping strategy allowed us to discover a number of other differentially expressed sncRNAs including piRNAs, lncRNAs, sn/snoRNAs, rRNAs, miscRNAs and nonsense-mediated decay RNAs. We believe that our sncRNA analysis workflow is extremely comprehensive and suitable for discovery of novel sncRNAs changes, which may lead to the development of innovative diagnostic and therapeutic tools for TNBC.

摘要

癌症是美国第二大死因，也是全球主要的公共卫生问题。基础、临床和流行病学研究正在改善癌症的检测、预防和治疗效果。最近的技术进步使得能够对全基因组基因表达进行无偏且全面的筛选。小型非编码RNA（sncRNAs）已被证明在生物过程中发挥重要作用，并可作为特定疾病的诊断、预后和治疗生物标志物。最近的研究结果开始揭示并加深我们对sncRNA表达复杂结构的理解，包括微小RNA（miRNAs）、PIWI相互作用RNA（piRNAs）、长链非编码RNA（lncRNAs）、小核仁RNA（sn/snoRNAs）以及它们与生物系统的关系。我们使用了公开可用的小RNA测序数据，这些数据来自24个三阴性乳腺癌（TNBC）和14个相邻正常组织样本，以重新映射各种类型的sncRNAs。我们发现，与相邻正常组织相比，TNBC样本中共有55种miRNAs异常表达（p<0.005）（8种miRNAs上调；47种下调），而原研究仅报道了25种新的miRNAs。在本研究中，我们对差异表达的miRNAs进行了通路分析，结果显示TGF-β信号通路在TNBC样本中受到显著影响。此外，我们全面的重新映射策略使我们能够发现许多其他差异表达的sncRNAs，包括piRNAs、lncRNAs、sn/snoRNAs、核糖体RNA（rRNAs）、杂项RNA（miscRNAs）和无义介导的衰变RNA。我们相信，我们的sncRNA分析工作流程极其全面，适用于发现新的sncRNAs变化，这可能会导致开发针对TNBC的创新诊断和治疗工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/316e/5370502/ae8d6df1324a/jcav08p0578g024.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/316e/5370502/ae8d6df1324a/jcav08p0578g024.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/316e/5370502/88a2d25c855c/jcav08p0578g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/316e/5370502/e6085aa6875b/jcav08p0578g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/316e/5370502/0158733d540b/jcav08p0578g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/316e/5370502/2b5a904a6821/jcav08p0578g017.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/316e/5370502/ae8d6df1324a/jcav08p0578g024.jpg

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