J Genomics 2017; 5:16-31. doi:10.7150/jgen.18856 This volume

Research Paper

Exploration of small RNA-seq data for small non-coding RNAs in Human Colorectal Cancer

Srinivas V Koduru1✉, Amit K Tiwari2, Sprague W Hazard3, Milind Mahajan4, Dino J Ravnic1

1. Division of Plastic Surgery, Department of Surgery, College of Medicine, Pennsylvania State University, Hershey, PA, USA;
2. Department of Pharmacology & Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo - Health Sciences Campus, Toledo, OH, USA;
3. Department of Anesthesia, College of Medicine, Pennsylvania State University, Hershey, PA, USA;
4. Genomics Facility, Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

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Koduru SV, Tiwari AK, Hazard SW, Mahajan M, Ravnic DJ. Exploration of small RNA-seq data for small non-coding RNAs in Human Colorectal Cancer. J Genomics 2017; 5:16-31. doi:10.7150/jgen.18856. Available from https://www.jgenomics.com/v05p0016.htm

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Graphic abstract

Background: 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. Results: 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. Conclusion: 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.

Keywords: Bioinformatics, colorectal cancer, next-generation genomic sequencing, small non-coding RNA, sncRNA, miRNA, snoRNA.