Alu siRNA to increase Alu element methylation and prevent DNA damage

被引：36

作者：

Patchsung, Maturada ^{[1
]}

Settayanon, Sirapat ^{[2
]}

Pongpanich, Monnat ^{[3
,4
,5
]}

Mutirangura, Dharm ^{[4
]}

Jintarith, Pornrutsami ^{[6
]}

Mutirangura, Apiwat ^{[4
,7
]}

机构：

[1] Chulalongkorn Univ, Fac Grad Sch, Interdept Program Biomed Sci, Bangkok, Thailand

[2] Chulalongkorn Univ, Program Med Sci, Fac Med, Bangkok, Thailand

[3] Chulalongkorn Univ, Dept Math & Comp Sci, Fac Sci, Bangkok, Thailand

[4] Chulalongkorn Univ, Ctr Excellence Mol Genet Canc & Human Dis, Bangkok, Thailand

[5] Chulalongkorn Univ, Omics Sci & Bioinformat Ctr, Fac Sci, Bangkok, Thailand

[6] Mahidol Univ, Fac Trop Med, Dept Trop Nutr & Food Sci, Bangkok, Thailand

[7] Chulalongkorn Univ, Dept Anat, Fac Med, Bangkok, Thailand

来源：

EPIGENOMICS | 2018年 / 10卷 / 02期

关键词：

8-hydroxy-2 '-deoxyguanosine; aging; Alu interspersed repetitive element; Alu methylation; cancer; DNA damage; endogenous DNA damage; genomic instability; global DNA hypomethylation; RNA directed DNA methylation; DOUBLE-STRAND BREAKS; CPG METHYLATION; HUMAN CANCER; HYPOMETHYLATION; RNA; INSTABILITY; CELLS; PATTERNS; REPAIR; P53;

D O I：

10.2217/epi-2017-0096

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Global DNA hypomethylation promoting genomic instability leads to cancer and deterioration of human health with age. Aim: To invent a biotechnology that can reprogram this process. Methods: We used Alu siRNA to direct Alu interspersed repetitive sequences methylation in human cells. We evaluated the correlation between DNA damage and Alu methylation levels. Results: We observed an inverse correlation between Alu element methylation and endogenous DNA damage in white blood cells. Cells transfected with Alu siRNA exhibited high Alu methylation levels, increased proliferation, reduced endogenous DNA damage and improved resistance to DNA damaging agents. Conclusion: Alu methylation stabilizes the genome by preventing accumulation of DNA damage. Alu siRNA could be useful for evaluating reprograming of the global hypomethylation phenotype in cancer and aging cells.

引用

页码：175 / 185

页数：11

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