J Cancer 2017; 8(4):578-596. doi:10.7150/jca.17633
A Comprehensive NGS Data Analysis of Differentially Regulated miRNAs, piRNAs, lncRNAs and sn/snoRNAs in Triple Negative Breast Cancer
1. Division of Plastic Surgery, Department of Surgery, College of Medicine, Pennsylvania State University, 500 University Drive, Hershey, PA 17033;
2. Department of Pharmacology & Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo - Health Sciences Campus, 300 Arlington Ave, Toledo, OH 43614;
3. Department of Anesthesia, College of Medicine, Pennsylvania State University, 500 University Drive, Hershey, PA 17033;
4. Department of Pharmacology, Department of Biochemistry and Molecular Biology, and Institute for Personalized Medicine, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA17033;
5. Genomics Facility, Department of Genetics and Genomics Sciences, Icahn School of Medicine, Mount Sinai, 1425 Madison Ave, New York, NY 10029.
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.
Keywords: sncRNA, TNBC, breast cancer, NGS, snoRNA, miRNA, piRNA
Koduru SV, Tiwari AK, Leberfinger A, Hazard SW, Kawasawa YI, Mahajan M, Ravnic DJ. A Comprehensive NGS Data Analysis of Differentially Regulated miRNAs, piRNAs, lncRNAs and sn/snoRNAs in Triple Negative Breast Cancer. J Cancer 2017; 8(4):578-596. doi:10.7150/jca.17633. Available from http://www.jcancer.org/v08p0578.htm