Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.
Department of Biology, University of Bari Aldo Moro, Bari, Italy.
Mol Cancer. 2020 Mar 30;19(1):69. doi: 10.1186/s12943-020-01187-5.
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.
非编码 RNA（ncRNAs）通过影响关键肿瘤抑制基因和癌基因的表达，成为人类致癌作用的调控因子。它们根据长度分为短链和长链 ncRNAs。环状 RNA（circRNAs）属于第二类，最近被发现是由反向剪接产生的，连接一个或多个外显子，或带有保留内含子的外显子。人浆细胞瘤变异易位 1（PVT1）基因位于染色体 8 号长臂（8q24）上，编码 52 个 ncRNAs 变体，包括 26 个线性和 26 个环状异构体，以及 6 个 microRNAs。PVT1 基因组座位于 MYC 的下游 54 Kb 处，并且这两个基因之间已经描述了几种相互作用，包括反馈调节机制。还报道了 PVT1/circPVT1 的 MYC 非依赖性功能，特别是在免疫反应的调节中。在这里，我们综述并讨论了 PVT1 和 circPVT1 在造血系统中的作用。目前尚无关于它们在造血细胞中转化能力的信息。然而，现有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/或转录增加而上调，为急性髓性白血病、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：在临床前肿瘤模型中，髓源抑制细胞中线性形式的过度表达诱导免疫耐受，circPVT1 在髓样和淋巴样细胞亚群中表现出免疫抑制特性。总的来说，这些关于 PVT1 和 circPVT1 在血液恶性肿瘤和免疫反应中的功能的最新数据反映了同一枚硬币的两面：通过促进恶性细胞更具侵袭性的表型参与癌症进展，以及作为一种新的潜在治疗耐药机制的免疫系统负调节。
