ADAR1-mediated RNA-editing of 3'UTRs in breast cancer.
ADAR1-mediated RNA-editing of 3'UTRs in breast cancer.
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DOI：
10.1186/s40659-018-0185-4
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发表时间：
2018-10-05
影响因子：
6.7
通讯作者：
Armisén R
中科院分区：
文献类型：
--
作者：
Sagredo EA;Blanco A;Sagredo AI;Pérez P;Sepúlveda-Hermosilla G;Morales F;Müller B;Verdugo R;Marcelain K;Harismendy O;Armisén R
对整个转录组RNA的变异分析表明，作用于RNA的腺苷脱氨酶(ADAR)酶修饰了很大一部分细胞RNA，促进了转录组的多样性和癌症的进化。尽管对ADAR在乳腺癌中的功能的了解取得了进展，但ADAR RNA编辑的功能后果还没有得到充分的解决。我们鉴定了81个乳腺细胞系中A到G(I)的mRNA编辑，显示与永生化的非恶性细胞系相比，乳腺癌细胞中3‘非编码区和外显子区域的编辑增加。此外，BRCA TCGA队列中的肿瘤在查看ADAR1靶向的571个具有良好特征的UTRs时，编辑次数比正常乳腺样本增加了24%。ADAR1mRNA高表达的基底细胞样亚型乳腺癌患者的临床预后较差，其3‘UTRs的编辑增加。有趣的是，肿瘤中ATM、GINS4和POLH转录本的3‘UTRs的编辑量尤其增加，这与它们的mRNA表达有关。我们利用乳腺癌细胞系(ZR-75-1)中的shRNA证实了ADAR1在这一调控中的作用。总之，这些结果揭示了癌症相关途径相关基因的mRNA编辑与临床结果之间的显著关联，表明ADAR1的表达和功能在乳腺癌中发挥着重要作用。本文的在线版本(10.1186/s40659-0180185-4)包含补充材料，可供授权用户使用。
Whole transcriptome RNA variant analyses have shown that adenosine deaminases acting on RNA (ADAR) enzymes modify a large proportion of cellular RNAs, contributing to transcriptome diversity and cancer evolution. Despite the advances in the understanding of ADAR function in breast cancer, ADAR RNA editing functional consequences are not fully addressed. We characterized A to G(I) mRNA editing in 81 breast cell lines, showing increased editing at 3′UTR and exonic regions in breast cancer cells compared to immortalized non-malignant cell lines. In addition, tumors from the BRCA TCGA cohort show a 24% increase in editing over normal breast samples when looking at 571 well-characterized UTRs targeted by ADAR1. Basal-like subtype breast cancer patients with high level of ADAR1 mRNA expression shows a worse clinical outcome and increased editing in their 3′UTRs. Interestingly, editing was particularly increased in the 3′UTRs of ATM, GINS4 and POLH transcripts in tumors, which correlated with their mRNA expression. We confirmed the role of ADAR1 in this regulation using a shRNA in a breast cancer cell line (ZR-75-1). Altogether, these results revealed a significant association between the mRNA editing in genes related to cancer-relevant pathways and clinical outcomes, suggesting an important role of ADAR1 expression and function in breast cancer. The online version of this article (10.1186/s40659-018-0185-4) contains supplementary material, which is available to authorized users.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
ADAR1结合的基因组分析及其参与多个RNA处理途径。
影响因子：
16.6
作者：
Bahn, Jae Hoon;Ahn, Jaegyoon;Lin, Xianzhi;Zhang, Qing;Lee, Jae-Hyung;Civelek, Mete;Xiao, Xinshu
通讯作者：
Xiao, Xinshu
影响因子：
3.5
作者：
Galipon J;Ishii R;Suzuki Y;Tomita M;Ui-Tei K
通讯作者：
Ui-Tei K
影响因子：
7.4
作者：
Crews LA;Jiang Q;Zipeto MA;Lazzari E;Court AC;Ali S;Barrett CL;Frazer KA;Jamieson CH
通讯作者：
Jamieson CH
ADAR1 通过以催化独立的方式调节 microRNA 加工来实现分化和神经诱导
影响因子：
44.1
作者：
Chen, Tian;Xiang, Jian-Feng;Chen, Ling-Ling
通讯作者：
Chen, Ling-Ling