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Abstract
Non coding RNAs (ncRNAs) have emerged as regulators of human carcinogenesis by affecting the expression of key tumor suppressor genes and oncogenes. They are divided into short and long ncRNAs, according to their length. Circular RNAs (circRNAs) are included in the second group and were recently discovered as being originated by back-splicing, joining either single or multiple exons, or exons with retained introns. The human Plasmacytoma Variant Translocation 1 (PVT1) gene maps on the long arm of chromosome 8 (8q24) and encodes for 52 ncRNAs variants, including 26 linear and 26 circular isoforms, and 6 microRNAs. PVT1 genomic locus is 54 Kb downstream to MYC and several interactions have been described among these two genes, including a feedback regulatory mechanism. MYC-independent functions of PVT1/circPVT1 have been also reported, especially in the regulation of immune responses. We here review and discuss the role of both PVT1 and circPVT1 in the hematopoietic system. No information is currently available concerning their transforming ability in hematopoietic cells. However, present literature supports their cooperation with a more aggressive and/or undifferentiated cell phenotype, thus contributing to cancer progression. PVT1/circPVT1 upregulation through genomic amplification or rearrangements and/or increased transcription, provides a proliferative advantage to malignant cells in acute myeloid leukemia, acute promyelocytic leukemia, Burkitt lymphoma, multiple myeloma (linear PVT1) and acute lymphoblastic leukemia (circPVT1). In addition, PVT1 and circPVT1 regulate immune responses: the overexpression of the linear form in myeloid derived suppressor cells induced immune tolerance in preclinical tumor models and circPVT1 showed immunosuppressive properties in myeloid and lymphoid cell subsets. Overall, these recent data on PVT1 and circPVT1 functions in hematological malignancies and immune responses reflect two faces of the same coin: involvement in cancer progression by promoting a more aggressive phenotype of malignant cells and negative regulation of the immune system as a novel potential therapy-resistance mechanism.
Highlights
Non-coding RNAs are transcripts that do not encode proteins
Some Non coding RNA (ncRNA) have a tumor suppressor function while others act as oncogenes [3, 4]. ncRNAs are classified into two categories on the basis of the length of their sequence: short ncRNAs do not exceed 200 nucleotides in size, while long ncRNAs are characterized by longer sequences
By comparing transcripts correlated with Plasmacytoma Variant Translocation 1 (PVT1) expression across myeloid and B cell malignancies we identified a core of 169 common genes, showing a positive or negative correlation with PVT1 (Spearman q ≤ 0.05, Additional file 1)
Summary
Non-coding RNAs (ncRNAs) are transcripts that do not encode proteins. They are diffused in the human genome and dysregulated in cancer cells. Human Plasmacytoma Variant Translocation 1 (PVT1) gene is located on chromosome band 8q24.21 (Fig. 1) and encodes for both circRNAs and linear ncRNA isoforms, as well as 6 microRNAs. In this review, we describe the currently available data on the role of both PVT1 and circPVT1 in hematopoietic cells and especially in hematological
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