Crosstalk Between MYC and lncRNAs in Hematological Malignancies.
Crosstalk Between MYC and lncRNAs in Hematological Malignancies.
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DOI：
10.3389/fonc.2020.579940
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发表时间：
2020
影响因子：
4.7
通讯作者：
Möröy T
中科院分区：
文献类型：
--
作者：
Arman K;Möröy T
人类基因组计划揭示了数千种长链非编码rna （lncrna）的存在。这些转录本长度超过200个核苷酸，它们在调节基因表达方面的重要性很快被认识到。然而，它们在物种间的保护程度较差，其注释仍存在争议，这在一定程度上限制了它们的研究。此外，与蛋白质编码基因相比，lncrna的表达普遍较低，其神秘的生化机制阻碍了对其生物学作用的理解。然而，众所周知，lncrna参与各种相互作用，并可与其他rna形成复合物，基因组DNA或蛋白质使其功能调控网络非常复杂。最近的研究表明，lncRNAs在基因表达中发挥重要作用，影响许多细胞发育、细胞分化的过程，也影响白血病和淋巴瘤等血癌的发病机制。许多lncrna已被发现受几种众所周知的转录因子调控，包括髓细胞瘤病病毒癌基因同源物（MYC）。众所周知，c-MYC基因是最常被解除管制的致癌基因之一，也是许多人类癌症的驱动因素。在造血癌症中，c-MYC基因经常被染色体易位激活，尤其是在B细胞或t细胞淋巴瘤或白血病中，人们对其作为DNA结合转录调节因子的作用已经了解得很多。尽管对MYC在血癌中控制lncRNA表达的调控作用以及MYC本身如何受lncRNA控制的理解仍处于起步阶段，但一幅有趣的图景表明，c-MYC可能通过lncRNA执行部分致癌功能。一些研究已经确定了不同血癌中调节c-MYC表达的lncrna和c-MYC调节的lncrna，并揭示了这些RNA分子如何起作用的新机制。在这篇综述中，我们概述了在白血病和淋巴瘤活化c-MYC的背景下被认为是关键的lncrna，描述了它们的作用机制和它们对癌细胞转录重编程的影响。最后，我们讨论了干扰它们的分子功能如何被用于新的癌症治疗的可能方法。
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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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
3
作者：
Cheng, P.;Lu, P.;Cheng, H.
通讯作者：
Cheng, H.
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
影响因子：
64.5
作者：
Atianand MK;Hu W;Satpathy AT;Shen Y;Ricci EP;Alvarez-Dominguez JR;Bhatta A;Schattgen SA;McGowan JD;Blin J;Braun JE;Gandhi P;Moore MJ;Chang HY;Lodish HF;Caffrey DR;Fitzgerald KA
通讯作者：
Fitzgerald KA
影响因子：
3.9
作者：
Andresini, Oriella;Rossi, Marianna Nicoletta;Maione, Rossella
通讯作者：
Maione, Rossella