Linear and circular PVT1 in hematological malignancies and immune response: two faces of the same coin

Ghetti, Martina; Vannini, Ivan; Storlazzi, Clelia Tiziana; Martinelli, Giovanni; Simonetti, Giorgia

doi:10.1186/s12943-020-01187-5

Cited by 59 publications

(64 citation statements)

References 126 publications

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Section: Lncrnas That Alter Myc Activitymentioning

confidence: 99%

“…Another intriguing property of the PVT1 gene locus is the fact that it also encodes a circular RNA called circPVT1 ( Figure 3 ) with 26 different isoforms ( 114 ). The most common isoform which has the highest level of expression in blood cells includes the whole exon 2 of PVT 1, which forms a closed loop-like structure ( 114 – 116 ). Circular RNAs (circRNAs) have been identified as a new class of non-coding RNAs which are well conserved, widespread, abundant and are regulated independently of their cognate linear isoform in the eukaryotic transcriptome ( 115 , 117 , 118 ).…”

Section: Lncrnas That Alter Myc Activitymentioning

confidence: 99%

“…These are generally formed by back-splicing of pre-mRNA and form a closed loop structure in which their 3′ and 5′ ends are covalently linked conferring them an increased stability and resistance ( 115 , 119 , 120 ). LncRNA PVT1 and circPVT1 regulate their expression independently of each other as they arise from separate individual promoters and have different genome localizations ( 114 , 121 , 122 ). The role of circPVT1 and PVT1 in different hematological malignancies with downstream deregulation of MYC has been very well highlighted in a recent review by Ghetti et al ( 114 ).…”

Section: Lncrnas That Alter Myc Activitymentioning

confidence: 99%

“…LncRNA PVT1 and circPVT1 regulate their expression independently of each other as they arise from separate individual promoters and have different genome localizations ( 114 , 121 , 122 ). The role of circPVT1 and PVT1 in different hematological malignancies with downstream deregulation of MYC has been very well highlighted in a recent review by Ghetti et al ( 114 ). circPVT1 is well studied in ALL in which the authors demonstrate that circPVT1 (but not PVT1 ) was specifically highly expressed in human patient samples of ALL but not AML samples as compared to healthy control groups ( 123 ).…”

Section: Lncrnas That Alter Myc Activitymentioning

confidence: 99%

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Crosstalk Between MYC and lncRNAs in Hematological Malignancies

Arman

Möröy

2020

Front. Oncol.

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The human genome project revealed the existence of many thousands of long non-coding RNAs (lncRNAs). These transcripts that are over 200 nucleotides long were soon recognized for their importance in regulating gene expression. However, their poor conservation among species and their still controversial annotation has limited their study to some extent. Moreover, a generally lower expression of lncRNAs as compared to protein coding genes and their enigmatic biochemical mechanisms have impeded progress in the understanding of their biological roles. It is, however, known that lncRNAs engage in various kinds of interactions and can form complexes with other RNAs, with genomic DNA or proteins rendering their functional regulatory network quite complex. It has emerged from recent studies that lncRNAs exert important roles in gene expression that affect many cellular processes underlying development, cellular differentiation, but also the pathogenesis of blood cancers like leukemia and lymphoma. A number of lncRNAs have been found to be regulated by several well-known transcription factors including Myelocytomatosis viral oncogene homolog ( MYC ). The c-MYC gene is known to be one of the most frequently deregulated oncogenes and a driver for many human cancers. The c- MYC gene is very frequently activated by chromosomal translocations in hematopoietic cancers most prominently in B- or T-cell lymphoma or leukemia and much is already known about its role as a DNA binding transcriptional regulator. Although the understanding of MYC’s regulatory role controlling lncRNA expression and how MYC itself is controlled by lncRNA in blood cancers is still at the beginning, an intriguing picture emerges indicating that c-MYC may execute part of its oncogenic function through lncRNAs. Several studies have identified lncRNAs regulating c- MYC expression and c-MYC regulated lncRNAs in different blood cancers and have unveiled new mechanisms how these RNA molecules act. In this review, we give an overview of lncRNAs that have been recognized as critical in the context of activated c-MYC in leukemia and lymphoma, describe their mechanism of action and their effect on transcriptional reprogramming in cancer cells. Finally, we discuss possible ways how an interference with their molecular function could be exploited for new cancer therapies.

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Section: Lncrnas That Alter Myc Activitymentioning

confidence: 99%

Section: Lncrnas That Alter Myc Activitymentioning

confidence: 99%

Section: Lncrnas That Alter Myc Activitymentioning

confidence: 99%

Section: Lncrnas That Alter Myc Activitymentioning

confidence: 99%

See 2 more Smart Citations

Crosstalk Between MYC and lncRNAs in Hematological Malignancies

Arman

Möröy

2020

Front. Oncol.

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“…Молекулы РНК этого класса широко вовлечены в регуляцию дифференцировки и функционирования иммунных клеток в нормальных и патологических условиях. Так, высокий уровень PVT1 обнаруживается в моноцитах, CD4+ и CD8+ T-лимфоцитах в норме, а его патологическое повышение наблюдается у пациентов с острой и хронической лейкемией, множественной миеломой и рядом других опухолевых заболеваний [15,16]. В последние годы начали появляться данные о связи уровня PVT1 и с различными аутоиммунными заболеваниями, такими как системная красная волчанка и ревматоидный артрит [17,18].…”

Section: ч а с т о т ы н о с и т е л ь с т в а а л л е л е й и г е н unclassified

Polymorphic variants in the PVT1 locus affect multiple sclerosis severity

Kiselev

Kozin

Baulina

et al. 2020

RJTAO

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Multiple sclerosis (MS) is a chronic autoimmune disease, in the pathogenesis of which the concurrence of demyelination of central nervous system (CNS) axons and neurodegeneration plays a role and which is accompanied by progressive neurological dysfunction. Long-term monitoring of patients with MS is needed to rate its severity according to existing scales; it is therefore very relevant to search for genomic markers that can predict the rate of disease progression at early stages. The impact of polymorphic variants in the PVT1 locus on MS severity has not been previously studied.Objective: to analyze the association of the polymorphic variants rs4645948 in the MYC gene and rs2114358 and rs4410871) in the PVT1 genes with MS severity according to the Multiple Sclerosis Severity Scale (MSSS) separately and as part of biallelic combinations, as well as the possible linkage disequilibrium of the studied single nucleotide polymorphisms for establishing the independence of the observed associations.Patients and methods. The investigation enrolled 468 Russian MS patients who did not take immunomodulating drugs before blood testing. The patients were divided into two groups: 1) relatively mild MS (MSSS ≤3.5) and 2) relatively severe MS (MSSS >3.5). The polymorphic variants in the PVT1 locus were genotyped by a real-time polymerase chain reaction assay.Results and discussion. In the MS study group, the carriage of the allele of PVT1 (rs2114358)*G turned out to be associated with the severe course of the disease (pf=0.042; odds ratio (OR)=1.41). The significance of the association increases in the simultaneous carriage of this allele with another variant of the same gene – PVT1 (rs4410871)*T (pf=0.024; OR=1.58). There was no linkage disequilibrium between the components of the biallelic combination.Conclusion. The polymorphic variants in the PVT1 locus are associated with the severity of MS.

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