Koduru Srinivas V, Tiwari Amit K, Hazard Sprague W, Mahajan Milind, Ravnic Dino J
Division of Plastic Surgery, Department of Surgery, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
Department of Pharmacology & Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo - Health Sciences Campus, Toledo, OH, USA.
J Genomics. 2017 Feb 28;5:16-31. doi: 10.7150/jgen.18856. eCollection 2017.
Improved healthcare and recent breakthroughs in technology have substantially reduced cancer mortality rates worldwide. Recent advancements in next-generation sequencing (NGS) have allowed genomic analysis of the human transcriptome. Now, using NGS we can further look into small non-coding regions of RNAs (sncRNAs) such as microRNAs (miRNAs), Piwi-interacting-RNAs (piRNAs), long non-coding RNAs (lncRNAs), and small nuclear/nucleolar RNAs (sn/snoRNAs) among others. Recent studies looking at sncRNAs indicate their role in important biological processes such as cancer progression and predict their role as biomarkers for disease diagnosis, prognosis, and therapy. In the present study, we data mined publically available small RNA sequencing data from colorectal tissue samples of eight matched patients (benign, tumor, and metastasis) and remapped the data for various small RNA annotations. We identified aberrant expression of 13 miRNAs in tumor and metastasis specimens [tumor vs benign group (19 miRNAs) and metastasis vs benign group (38 miRNAs)] of which five were upregulated, and eight were downregulated, during disease progression. Pathway analysis of aberrantly expressed miRNAs showed that the majority of miRNAs involved in colon cancer were also involved in other cancers. Analysis of piRNAs revealed six to be over-expressed in the tumor vs benign cohort and 24 in the metastasis vs benign group. Only two piRNAs were shared between the two cohorts. Examining other types of small RNAs [sn/snoRNAs, mt_rRNA, miscRNA, nonsense mediated decay (NMD), and rRNAs] identified 15 sncRNAs in the tumor vs benign group and 104 in the metastasis vs benign group, with only four others being commonly expressed. In summary, our comprehensive analysis on publicly available small RNA-seq data identified multiple differentially expressed sncRNAs during colorectal cancer progression at different stages compared to normal colon tissue. We speculate that deciphering and validating the roles of sncRNAs may prove useful in colorectal cancer prognosis, diagnosis, and therapy.
医疗保健的改善以及近期的技术突破已大幅降低了全球癌症死亡率。下一代测序（NGS）的最新进展使得对人类转录组进行基因组分析成为可能。现在，利用NGS我们可以进一步研究RNA的小非编码区域（sncRNA），如微小RNA（miRNA）、Piwi相互作用RNA（piRNA）、长链非编码RNA（lncRNA）以及小核/核仁RNA（sn/snoRNA）等。近期对sncRNA的研究表明它们在诸如癌症进展等重要生物学过程中发挥作用，并预测它们作为疾病诊断、预后和治疗生物标志物的作用。在本研究中，我们挖掘了来自8例匹配患者（良性、肿瘤和转移）结直肠组织样本的公开可用小RNA测序数据，并对各种小RNA注释重新映射了数据。我们在肿瘤和转移标本中鉴定出13种miRNA的异常表达[肿瘤与良性组（19种miRNA）以及转移与良性组（38种miRNA）]，其中在疾病进展过程中有5种上调，8种下调。对异常表达的miRNA进行通路分析表明，大多数参与结肠癌的miRNA也参与其他癌症。对piRNA的分析显示，在肿瘤与良性队列中有6种过表达，在转移与良性组中有24种过表达。两个队列中仅共享两种piRNA。检查其他类型的小RNA[sn/snoRNA、mt_rRNA、miscRNA、无义介导衰变（NMD）和rRNA]，在肿瘤与良性组中鉴定出15种sncRNA，在转移与良性组中鉴定出104种sncRNA，只有另外4种是共同表达的。总之，我们对公开可用的小RNA测序数据的综合分析确定了与正常结肠组织相比，在结直肠癌不同阶段进展过程中有多种差异表达的sncRNA。我们推测，解读和验证sncRNA的作用可能对结直肠癌的预后、诊断和治疗有用。
