Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Department of Pancreaticobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Genome Med. 2021 Nov 19;13(1):183. doi: 10.1186/s13073-021-01002-w.
N-methyladenosine (mA) is the most abundant modification of RNA in eukaryotic cells and play critical roles in cancer. While most related studies focus on mA modifications in linear RNA, transcriptome-wide profiling and exploration of mA modification in circular RNAs in cancer is still lacking.
For the detection of mA modification in circRNAs, we developed a new bioinformatics tools called Circm6A and applied it to the mA-seq data of 77 tissue samples from 58 individuals with pancreatic ductal adenocarcinoma (PDAC).
Circm6A performs better than the existing circRNA identification tools, which achieved highest F1 score among these tools in the detection of circRNAs with mA modifications. By using Circm6A, we identified a total of 8807 mA-circRNAs from our mA-seq data. The mA-circRNAs tend to be hypermethylated in PDAC tumor tissues compared with normal tissues. The hypermethylated mA-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 mA-circRNAs may promote the circularization and translation of circRNAs.
These comprehensive findings further bridged the knowledge gaps between mA modification and circRNAs fields by depicting the mA-circRNAs genomic landscape of PDAC patients and revealed the emerging roles played by mA-circRNAs in pancreatic cancer. Circm6A is available at https://github.com/canceromics/circm6a .
N6-甲基腺苷（m6A）是真核细胞中 RNA 最丰富的修饰，在癌症中发挥着关键作用。虽然大多数相关研究都集中在线性 RNA 的 mA 修饰上，但在癌症中环状 RNA 的 mA 修饰的全转录组谱分析和探索仍然缺乏。
为了检测 circRNA 中的 mA 修饰，我们开发了一种名为 Circm6A 的新生物信息学工具，并将其应用于 58 名胰腺导管腺癌（PDAC）患者 77 个组织样本的 mA-seq 数据。
Circm6A 的性能优于现有的 circRNA 识别工具，在检测具有 mA 修饰的 circRNA 时，它在这些工具中实现了最高的 F1 分数。通过使用 Circm6A，我们从 mA-seq 数据中总共鉴定了 8807 个 mA-circRNAs。与正常组织相比，PDAC 肿瘤组织中的 mA-circRNAs 倾向于过度甲基化。过度甲基化的 mA-circRNAs 与 circRNA-mRNA 共表达网络的显著增益相关，导致许多重要的癌症相关途径失调。此外，我们发现了提示，过度甲基化的 mA-circRNAs 可能促进 circRNAs 的环化和翻译。
这些全面的发现通过描绘 PDAC 患者的 mA-circRNAs 基因组图谱，进一步弥合了 mA 修饰和 circRNAs 领域之间的知识空白，并揭示了 mA-circRNAs 在胰腺癌中的新兴作用。Circm6A 可在 https://github.com/canceromics/circm6a 获得。
Zotero 插件