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长非编码 RNA 与血液系统恶性肿瘤中 MYC 的关联。

Long non-coding RNAs and MYC association in hematological malignancies.

机构信息

Blood Bank, Preveza General Hospital, 48100, Preveza, Greece.

Department of Pharmacy, School of Health Sciences, University of Patras, Patras, Greece.

出版信息

Ann Hematol. 2020 Oct;99(10):2231-2242. doi: 10.1007/s00277-020-04166-4. Epub 2020 Jul 4.

Abstract

Long non-coding RNAs (lncRNAs) have an established role in cell biology. Among their functions is the regulation of hematopoiesis. They characterize the different stages of hematopoiesis in a more lineage-restricted expression pattern than coding mRNAs. They affect hematopoietic stem cell renewal, proliferation, and differentiation of committed progenitors by interacting with master regulators transcription factors. Among these transcription factors, MYC has a prominent role. Similar to MYC's transcriptional activation/amplification of protein coding genes, MYC also regulates lncRNAs' expression profile, while it is also regulated by lncRNAs. Both myeloid and lymphoid malignancies are prone to the association of MYC with lncRNAs. Such interaction inhibits apoptosis, enhances cell proliferation, deregulates metabolism, and promotes genomic instability and resistance to treatment. In this review, we discuss the recent findings that encompass the crosstalk between lncRNAs and describe the pathways that very probably have a pathogenetic role in both acute and chronic hematologic malignancies.

摘要

长链非编码 RNA(lncRNA)在细胞生物学中具有重要作用。它们的功能之一是调节造血。与编码 mRNA 相比,lncRNA 以更具谱系限制性的表达模式来表征造血的不同阶段。它们通过与主调控转录因子相互作用来影响造血干细胞的更新、增殖和定向祖细胞的分化。在这些转录因子中,MYC 起着突出的作用。与 MYC 对蛋白质编码基因的转录激活/扩增类似,MYC 还调节 lncRNA 的表达谱,同时也受 lncRNA 的调节。髓系和淋系恶性肿瘤都容易与 MYC 与 lncRNA 相关联。这种相互作用抑制细胞凋亡、增强细胞增殖、使代谢失调,并促进基因组不稳定性和对治疗的耐药性。在这篇综述中,我们讨论了最近的发现,包括 lncRNA 之间的串扰,并描述了这些通路在急性和慢性血液恶性肿瘤中很可能具有发病作用。

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