Dal Molin Anna, Bresolin Silvia, Gaffo Enrico, Tretti Caterina, Boldrin Elena, Meyer Lueder H, Guglielmelli Paola, Vannucchi Alessandro M, Te Kronnie Geertruij, Bortoluzzi Stefania
Department of Molecular Medicine, University of Padua, Padua, Italy.
Department of Women's and Children's Health, University of Padua, Padua, Italy.
Front Genet. 2019 Feb 13;10:88. doi: 10.3389/fgene.2019.00088. eCollection 2019.
Chromosomal translocations harbored by cancer genomes are important oncogenic drivers. In rearranged acute leukemia (MLLre) fuses with over 90 partner genes. Mechanistic studies provided clues of MLL fusion protein leukemogenic potential, but models failed to fully recapitulate the disease. Recently, expression of oncogenic fusion circular RNAs (f-circ) by fusion was proven. This discovery, together with emerging data on the importance and diversity of circRNAs formed the incentive to study the circRNAs of the recombinome. Through interactions with other RNAs, such as microRNAs, and with proteins, circRNAs regulate cellular processes also related to cancer development. CircRNAs can translate into functional peptides too. and most of the 90 translocation partners do express circRNAs and exploration of our RNA-seq dataset of sorted blood cell populations provided new data on alternative circular isoform generation and expression variability of circRNAs of the recombinome. Further, we provided evidence that rearrangements of and three of the main translocation partner genes can impact circRNA expression, supported also by preliminary observations in leukemic cells. The emerging picture underpins the view that circRNAs are worthwhile to be considered when studying MLLre leukemias and provides a new perspective on the impact of chromosomal translocations in cancer cells at large.
癌症基因组中存在的染色体易位是重要的致癌驱动因素。在重排急性白血病（MLLre）中，MLL与90多种伙伴基因融合。机制研究为MLL融合蛋白的致白血病潜力提供了线索，但模型未能完全重现该疾病。最近，已证实通过融合产生致癌融合环状RNA（f-circ）。这一发现，连同关于环状RNA重要性和多样性的新出现数据，激发了对MLL重组基因组环状RNA的研究。通过与其他RNA（如微小RNA）以及蛋白质相互作用，环状RNA调节与癌症发展相关的细胞过程。环状RNA也可以翻译成功能性肽。90种MLL易位伙伴基因中的大多数确实表达环状RNA，对我们分选血细胞群体的RNA测序数据集的探索提供了关于MLL重组基因组环状RNA的替代性环状异构体产生和表达变异性的新数据。此外，我们提供了证据表明MLL及其三个主要易位伙伴基因的重排可影响环状RNA表达，白血病细胞中的初步观察结果也支持这一点。这一新出现的情况支持了这样一种观点，即在研究MLLre白血病时环状RNA值得考虑，并为染色体易位对癌细胞的影响提供了一个新的视角。
