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.

LncRNA Profiling Reveals That the Deregulation of H19, WT1-AS, TCL6, and LEF1-AS1 Is Associated with Higher-Risk Myelodysplastic Syndrome

“…Further, we detected a significant increase in PVT1 lncRNA, particularly in MDS with del(5q). PVT1 usually confers oncogenic properties on different types of cancer, including AML, and functions as a mediator of the tumor-suppressive functions of p53 [ 17 ].…”

Long Noncoding RNA Plasmacytoma Variant Translocation 1 Is Increased in Multiple Myeloma and Correlates With Lower Induction Response

“…More recently, lnc-PVT1 has been reported to be dysregulated and act as a convincing diagnostic biomarker in patients with a variety of cancers, including melanoma, 22 pediatric malignancies, 23 and liver cancer. 24 However, limited evidences could be found about its role in patients with hematologic malignancies.…”

Disease-Causing Mutations and Rearrangements in Long Non-coding RNA Gene Loci

“…Thus, MYC activation alone is typically not sufficient to reinforce cell transformation programs and initiate tumorigenesis. Besides the MYC gene, the 8q24.21 region harbors the PVT1 lncRNA locus, expression of which is consequently elevated in various types of cancer tissues and cell lines as a result of amplifications and translocations (Boloix et al, 2019;Jin et al, 2019). A report by Tseng et al (2014) suggests that the gain of PVT1 lncRNA expression is required for the maintenance of high MYC protein levels and cancer cell proliferation.…”

“…Besides MYC, PVT1 was also shown to stabilize other cell proliferation and survival promoting proteins, such as KLF5 and STAT3 Zhao et al, 2018). Consequently, PVT1 was identified as a prognostic marker for cancer patient's overall survival, and elevated PVT1 expression was found to associate with advanced tumor severity stage according to the tumor-node-metastasis (TNM) classification scheme (Lu et al, 2017;Martini et al, 2017;He et al, 2018;Boloix et al, 2019). Interestingly, two alternative PVT1 transcriptional start sites were shown to serve as enhancer elements, directly regulating MYC gene expression independent of PVT1 lncRNA expression (Fulco et al, 2016).…”