Murmann Andrea E, Yu Jindan, Opal Puneet, Peter Marcus E
Department of Medicine, Division Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Department of Medicine, Division Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, IL 60611, USA.
Trends Cancer. 2018 Oct;4(10):684-700. doi: 10.1016/j.trecan.2018.08.004. Epub 2018 Sep 26.
Many neurodegenerative diseases are caused by unstable trinucleotide repeat (TNR) expansions located in disease-associated genes. siRNAs based on CAG repeat expansions effectively kill cancer cell lines in vitro through RNAi. They also cause significant reduction in tumor growth in a human ovarian cancer mouse model with no toxicity to the treated mice. This suggests that cancer cells are particularly sensitive to CAG TNR-derived siRNAs, and explains a reported inverse correlation between the length of CAG TNRs and reduced global cancer incidences in some CAG TNR diseases. This review discusses both mutant proteins and mutant RNAs as a cause of TNR diseases, with a focus on RNAi and its role in contributing to disease pathology and in suppressing cancer.
许多神经退行性疾病是由位于疾病相关基因中的不稳定三核苷酸重复（TNR）扩增引起的。基于CAG重复扩增的小干扰RNA（siRNA）通过RNA干扰在体外有效杀死癌细胞系。它们还能显著抑制人卵巢癌小鼠模型中的肿瘤生长，且对接受治疗的小鼠没有毒性。这表明癌细胞对CAG TNR衍生的siRNA特别敏感，并解释了在某些CAG TNR疾病中报道的CAG TNR长度与全球癌症发病率降低之间的负相关。本综述讨论了突变蛋白和突变RNA作为TNR疾病的病因，重点是RNA干扰及其在疾病病理形成和癌症抑制中的作用。
