PRMT5 regulates RNA m6A demethylation for doxorubicin sensitivity in breast cancer

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	PRMT5 regulates RNA m6A demethylation for doxorubicin sensitivity in breast cancer
	Wu, Y; Wang, Z; Han, L; Guo, ZH; Yan, BH; Guo, LL; Zhao, HD; Wei, MY; Hou, NN; Ye, J; Wang, Z; Shi, CH; Liu, SL; Chen, CS; Chen, SN; Wang, T; Yi, J; Zhou, JP; Yao, LB; Zhou, WX; Ling, R; Zhang, J
	2022
发表期刊	MOLECULAR THERAPY
ISSN	1525-0016
卷号	30 期号:7 页码:2603-2617
摘要	Cancer cells respond to various stressful conditions through the dynamic regulation of RNA m6A modification. Doxoru-bicin is a widely used chemotherapeutic drug that induces DNA damage. It is interesting to know whether cancer cells regulate the DNA damage response and doxorubicin sensitivity through RNA m6A modification. Here, we found that doxoru-bicin treatment significantly induced RNA m6A methylation in breast cancer cells in both a dose-and a time-dependent manner. However, protein arginine methyltransferase 5 (PRMT5) inhibited RNA m6A modification under doxorubicin treatment by enhancing the nuclear translocation of the RNA demethylase AlkB homolog 5 (ALKBH5), which was previously believed to be exclusively localized in the nucleus. Then, ALKBH5 removed the m6A methylation of BRCA1 for mRNA stabilization and further enhanced DNA repair compe-tency to decrease doxorubicin efficacy in breast cancer cells. Importantly, we identified the approved drug tadalafil as a novel PRMT5 inhibitor that could decrease RNA m6A methyl-ation and increase doxorubicin sensitivity in breast cancer. The strategy of targeting PRMT5 with tadalafil is a promising approach to promote breast cancer sensitivity to doxorubicin through RNA methylation regulation.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13696
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Wu, Y,Wang, Z,Han, L,et al. PRMT5 regulates RNA m6A demethylation for doxorubicin sensitivity in breast cancer[J]. MOLECULAR THERAPY,2022,30(7):2603-2617.
APA	Wu, Y.,Wang, Z.,Han, L.,Guo, ZH.,Yan, BH.,...&Zhang, J.(2022).PRMT5 regulates RNA m6A demethylation for doxorubicin sensitivity in breast cancer.MOLECULAR THERAPY,30(7),2603-2617.
MLA	Wu, Y,et al."PRMT5 regulates RNA m6A demethylation for doxorubicin sensitivity in breast cancer".MOLECULAR THERAPY 30.7(2022):2603-2617.

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