Long Non-coding RNA PVT1 as a Prognostic and Therapeutic Target in Pediatric Cancer

Abstract

In recent decades, biomedical research has focused on understanding the functionality of the human translated genome, which represents a minor part of all genetic information transcribed from the human genome. However, researchers have become aware of the importance of non-coding RNA species that constitute the vast majority of the transcriptome. In addition to their crucial role in tissue development and homeostasis, mounting evidence shows non-coding RNA to be deregulated and functionally contributing to the development and progression of different types of human disease including cancer both in adults and children. Small non-coding RNAs (i.e., microRNA) are in the vanguard of clinical research which revealed that RNA could be used as disease biomarkers or new therapeutic targets. Furthermore, many more expectations have been raised for long non-coding RNAs, by far the largest fraction of non-coding transcripts, and still fewer findings have been translated into clinical applications. In this review, we center on PVT1, a large and complex long non-coding RNA that usually confers oncogenic properties on different tumor types. We focus on the compilation of early advances in the field of pediatric tumors which often lags behind clinical improvements in adult tumors, and provide a rationale to continue studying PVT1 as a possible functional contributor to pediatric malignancies and as a potential prognostic marker or therapeutic target.

Keywords: 8q32; PVT1; epigenetic; lncRNA; pediatric cancer.

Figure 1

Graphical representation of the 8q24 genomic locus.

Figure 2

PVT1 expression comparing healthy tissues (green) with pediatric tumors (blue). PVT1 RNA expression levels were obtained from publicly-available Affymetrix expression array (u133p2) datasets using the “R2: Genomics Analysis and Visualization Platform” software. B cells (GSE12366), brain (GSE11882), muscle (GSE9103), colon (GSE8671), Ewing sarcoma (GSE34620), burkitt lymphoma (GSE26673), mantle cell lymphoma (GSE93291), rhabdomyosarcoma (GSE66533), ALL (GSE68720), neuroblastoma (GSE16476), osteosarcoma (GSE14827), ATRT (GSE70678), wilm's tumor (R2 ID: ps_avgpres_wilmsocg125_u133p2), ependymoma (GSE64415), glioma (GSE19578), medulloblastoma (R2 ID: ps_avgpres_mb500affym223_u133p2). a.u, Arbitraty units.

Figure 3

Kaplan-Meier survival curves based on PVT1 expression in different pediatric tumors. Kaplan-Meier plots were generated using the “R2: Genomics Analysis and Visualization Platform” software. Patient samples were split according to high (above median) or low (below median) PVT1 expression levels from the following datasets: Wilm's tumor (n = 148, R2 ID:ps_avgpres_wilmsocga148_u133a), neuroblastoma (n = 476, GSE45547), mantle cell lymphoma (n = 122, GSE93291), Ewing's sarcoma (n = 52, GSE17679), osteosarcoma (n = 88, GSE42352), and pediatric glioma (n = 47, SE19578).