Nonsense-Mediated mRNA Decay: Pathologies and the Potential for Novel Therapeutics

被引:34
作者
Pawlicka, Kamila [1 ]
Kalathiya, Umesh [2 ]
Alfaro, Javier [1 ,2 ]
机构
[1] Univ Edinburgh, Edinburgh Canc Res Ctr, Edinburgh EH4 2XU, Midlothian, Scotland
[2] Univ Gdansk, Int Ctr Canc Vaccine Sci, PL-80308 Gdansk, Poland
基金
英国医学研究理事会;
关键词
Nonsense-mediated mRNA decay; Premature termination codon; Cancer; Neoantigens; NMD inhibition; BETA-GLOBIN GENE; CAENORHABDITIS-ELEGANS; SMG5-SMG7; HETERODIMER; UPF1; PHOSPHORYLATION; MAMMALIAN-CELLS; SMALL MOLECULES; NMD; SURVEILLANCE; INHIBITION; MUTATIONS;
D O I
10.3390/cancers12030765
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Nonsense-mediated messenger RNA (mRNA) decay (NMD) is a surveillance pathway used by cells to control the quality mRNAs and to fine-tune transcript abundance. NMD plays an important role in cell cycle regulation, cell viability, DNA damage response, while also serving as a barrier to virus infection. Disturbance of this control mechanism caused by genetic mutations or dys-regulation of the NMD pathway can lead to pathologies, including neurological disorders, immune diseases and cancers. The role of NMD in cancer development is complex, acting as both a promoter and a barrier to tumour progression. Cancer cells can exploit NMD for the downregulation of key tumour suppressor genes, or tumours adjust NMD activity to adapt to an aggressive immune microenvironment. The latter case might provide an avenue for therapeutic intervention as NMD inhibition has been shown to lead to the production of neoantigens that stimulate an immune system attack on tumours. For this reason, understanding the biology and co-option pathways of NMD is important for the development of novel therapeutic agents. Inhibitors, whose design can make use of the many structures available for NMD study, will play a crucial role in characterizing and providing diverse therapeutic options for this pathway in cancer and other diseases.
引用
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页数:17
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