Genome-wide identification and characterization of circular RNA m6A modification in pancreatic cancer

被引:19
作者
Ye, Ying [1 ,2 ]
Feng, Weiyi [1 ,2 ]
Zhang, Jialiang [1 ,2 ]
Zhu, Kaiyu [1 ,2 ]
Huang, Xudong [1 ,2 ]
Pan, Ling [1 ,2 ]
Su, Jiachun [1 ,2 ]
Zheng, Yanfen [1 ,2 ]
Li, Rui [1 ,2 ]
Deng, Shuang [1 ,2 ]
Bai, Ruihong [1 ,2 ]
Zhuang, Lisha [1 ,2 ]
Wei, Lusheng [3 ]
Deng, Junge [1 ,2 ]
Li, Mei [4 ]
Chen, Rufu [5 ,6 ]
Lin, Dongxin [1 ,2 ,7 ,8 ]
Zuo, Zhixiang [1 ,2 ]
Zheng, Jian [1 ,2 ,8 ]
机构
[1] Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol South China, Guangzhou, Peoples R China
[2] Collaborat Innovat Ctr Canc Med, Guangzhou, Peoples R China
[3] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Pancreaticobiliary Surg, Guangzhou, Peoples R China
[4] Sun Yat Sen Univ, Dept Pathol, Canc Ctr, Guangzhou, Peoples R China
[5] Guangdong Prov Peoples Hosp, Guangzhou, Peoples R China
[6] Guangdong Acad Med Sci, Guangzhou, Peoples R China
[7] Chinese Acad Med Sci & Peking Union Med Coll, Dept Etiol & Carcinogenesis, Natl Canc Ctr, Natl Clin Res Ctr,Canc Hosp, Beijing, Peoples R China
[8] Nanjing Med Univ, Collaborat Innovat Ctr Canc Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Peoples R China
基金
中国国家自然科学基金;
关键词
m(6)A modification; Circular RNA; m(6)A-seq; Pancreatic cancer; METHYLATION; REVEALS; TRANSLATION; LANDSCAPE; PACKAGE; WRITERS; N6-METHYLADENOSINE; DIFFERENTIATION; BIOGENESIS; WIDESPREAD;
D O I
10.1186/s13073-021-01002-w
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: N-6-methyladenosine (m(6)A) is the most abundant modification of RNA in eukaryotic cells and play critical roles in cancer. While most related studies focus on m(6)A modifications in linear RNA, transcriptome-wide profiling and exploration of m(6)A modification in circular RNAs in cancer is still lacking. Methods: For the detection of m(6)A modification in circRNAs, we developed a new bioinformatics tools called Circm6A and applied it to the m(6)A-seq data of 77 tissue samples from 58 individuals with pancreatic ductal adenocarcinoma (PDAC). Results: Circm6A performs better than the existing circRNA identification tools, which achieved highest F1 score among these tools in the detection of circRNAs with m(6)A modifications. By using Circm6A, we identified a total of 8807 m(6)A-circRNAs from our m(6)A-seq data. The m(6)A-circRNAs tend to be hypermethylated in PDAC tumor tissues compared with normal tissues. The hypermethylated m(6)A-circRNAs were associated with a significant gain of circRNA-mRNA coexpression network, leading to the dysregulation of many important cancer-related pathways. Moreover, we found the cues that hypermethylated m(6)A-circRNAs may promote the circularization and translation of circRNAs. Conclusions: These comprehensive findings further bridged the knowledge gaps between m(6)A modification and circRNAs fields by depicting the m(6)A-circRNAs genomic landscape of PDAC patients and revealed the emerging roles played by m(6)A-circRNAs in pancreatic cancer. Circm6A is available at https://github.com/canceromics/circm6a.
引用
收藏
页数:19
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