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.

中文翻译：

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血液恶性肿瘤和免疫反应中的线性和圆形PVT1：同一枚硬币的两个面


非编码 RNA (ncRNA) 通过影响关键抑癌基因和癌基因的表达而成为人类致癌的调节因子。根据长度，它们分为短 ncRNA 和长 ncRNA。环状 RNA (circRNA) 属于第二组，最近发现其起源于反向剪接，连接单个或多个外显子，或带有保留内含子的外显子。人类浆细胞瘤变体易位 1 (PVT1) 基因定位在 8 号染色体长臂 (8q24) 上，编码 52 种 ncRNA 变体，包括 26 种线性和 26 种环状亚型以及 6 种 microRNA。 PVT1 基因组位点位于 MYC 下游 54 Kb，这两个基因之间的几种相互作用已被描述，包括反馈调节机制。 PVT1/circPVT1 的不依赖于 MYC 的功能也有报道，特别是在免疫反应的调节方面。我们在此回顾并讨论 PVT1 和 circPVT1 在造血系统中的作用。目前还没有关于它们在造血细胞中的转化能力的信息。然而，目前的文献支持它们与更具侵袭性和/或未分化的细胞表型合作，从而促进癌症进展。 PVT1/circPVT1 通过基因组扩增或重排和/或增加转录而上调，为急性髓系白血病、急性早幼粒细胞白血病、伯基特淋巴瘤、多发性骨髓瘤（线性 PVT1）和急性淋巴细胞白血病（circPVT1）中的恶性细胞提供增殖优势。 此外，PVT1和circPVT1调节免疫反应：髓源性抑制细胞中线性形式的过度表达在临床前肿瘤模型中诱导免疫耐受，并且circPVT1在髓系和淋巴细胞亚群中显示出免疫抑制特性。总体而言，这些关于 PVT1 和 circPVT1 在血液恶性肿瘤和免疫反应中功能的最新数据反映了同一枚硬币的两个方面：通过促进恶性细胞更具侵袭性的表型来参与癌症进展，以及作为一种新型潜在疗法对免疫系统进行负调节。抵抗机制。