| Autor: |
Rajasekaran S; Department of Molecular Genetics, The Ohio State University, Columbus, OH, United States.; The Ohio State University Comprehensive Cancer Center, Columbus, OH,, United States.; Center for RNA Biology, The Ohio State University, Columbus, OH, United States., Nagarajha Selvan LD; Department of Nanobiotechnology, Vision Research Foundation, Sankara Nethralaya, Chennai, India., Dotts K; Department of Molecular Genetics, The Ohio State University, Columbus, OH, United States.; The Ohio State University Comprehensive Cancer Center, Columbus, OH,, United States.; Center for RNA Biology, The Ohio State University, Columbus, OH, United States., Kumar R; Department of Nanobiotechnology, Vision Research Foundation, Sankara Nethralaya, Chennai, India., Rishi P; Shri Bhagwan Mahavir Vitreoretinal Services and Ocular Oncology Services, Medical Research Foundation, Sankara Nethralaya, Chennai, India., Khetan V; Shri Bhagwan Mahavir Vitreoretinal Services and Ocular Oncology Services, Medical Research Foundation, Sankara Nethralaya, Chennai, India., Bisht M; Department of Molecular Genetics, The Ohio State University, Columbus, OH, United States.; The Ohio State University Comprehensive Cancer Center, Columbus, OH,, United States.; Center for RNA Biology, The Ohio State University, Columbus, OH, United States., Sivaraman K; MedGenome, Bangalore, India., Krishnakumar S; L&T Department of Ocular Pathology, Vision Research Foundation, Chennai, India., Sahoo D; Department of Pediatrics and Department of Computer Science and Engineering, University of California, San Diego, San Diego, CA, United States., Campbell MJ; Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, United States., Elchuri SV; Department of Nanobiotechnology, Vision Research Foundation, Sankara Nethralaya, Chennai, India., Miles WO; Department of Molecular Genetics, The Ohio State University, Columbus, OH, United States.; The Ohio State University Comprehensive Cancer Center, Columbus, OH,, United States.; Center for RNA Biology, The Ohio State University, Columbus, OH, United States. |
| Abstrakt: |
Retinoblastoma is a rare pediatric tumor of the retina, caused by the homozygous loss of the Retinoblastoma 1 (RB1) tumor suppressor gene. Previous microarray studies have identified changes in the expression profiles of coding genes; however, our understanding of how non-coding genes change in this tumor is absent. This is an important area of research, as in many adult malignancies, non-coding genes including LNC-RNAs are used as biomarkers to predict outcome and/or relapse. To establish a complete and in-depth RNA profile, of both coding and non-coding genes, in Retinoblastoma tumors, we conducted RNA-seq from a cohort of tumors and normal retina controls. This analysis identified widespread transcriptional changes in the levels of both coding and non-coding genes. Unexpectedly, we also found rare RNA fusion products resulting from genomic alterations, specific to Retinoblastoma tumor samples. We then determined whether these gene expression changes, of both coding and non-coding genes, were also found in a completely independent Retinoblastoma cohort. Using our dataset, we then profiled the potential effects of deregulated LNC-RNAs on the expression of neighboring genes, the entire genome, and on mRNAs that contain a putative area of homology. This analysis showed that most deregulated LNC-RNAs do not act locally to change the transcriptional environment, but potentially function to modulate genes at distant sites. From this analysis, we selected a strongly down-regulated LNC-RNA in Retinoblastoma, DRAIC, and found that restoring DRAIC RNA levels significantly slowed the growth of the Y79 Retinoblastoma cell line. Collectively, our work has generated the first non-coding RNA profile of Retinoblastoma tumors and has found that these tumors show widespread transcriptional deregulation. |
