Mei Yue, Liang Dong, Ai Bin, Wang Tengjiao, Guo Shiwei, Jin Gang, Yu Dong
Department of Precision Medicine, Translational Medicine Research Center, Naval Medical University, Shanghai, China.
Shanghai Key Laboratory of Cell Engineering, Shanghai, China.
Front Oncol. 2023 Feb 21;13:1092046. doi: 10.3389/fonc.2023.1092046. eCollection 2023.
RNA editing, a wide-acknowledged post-transcriptional mechanism, has been reported to be involved in the occurrence and development of cancer, especially the abnormal alteration of adenosine to inosine. However, fewer studies focus on pancreaticcancer. Therefore, we aimed to explore the possible linkages between altered RNA editing events and the development of PDAC.
We characterized the global A-to-I RNA editing spectrum from RNA and matched whole-genome sequencing data of 41 primary PDAC and adjacent normal tissues. The following analyses were performed: different editing level and RNA expression analysis,pathway analysis, motif analysis, RNA secondary structure analysis, alternative splicing events analysis, and survival analysis.The RNA editing of single-cell RNA public sequencing data was also characterized.
A large number of adaptive RNA editing events with significant differences in editing levels were identified, which are mainly regulated by ADAR1. Moreover, RNA editing in tumors has a higher editing level and more abundant editing sites in general. 140genes were screened out since they were identified with significantly different RNA editing events and were significantly different in expression level between tumor and matched normal samples. Further analysis showed a preference that in the tumor-specific group, they are mainly enriched in cancer-related signal pathways, while in the normal tissue-specific group, they are mainly enriched in pancreatic secretion. At the same time, we also found positively selected differentially edited sites in a series of cancer immune genes, including EGF, IGF1R, and PIK3CD. RNA editing might participate in pathogenisis of PDAC through regulating the alternative splicing and RNA secondary structure of important genesto further regulate gene expression and protein synthesis, including RAB27B and CERS4. Furthermore, single cell sequencing results showed that type2 ductal cells contributed the most to RNA editing events in tumors.
RNA editing is an epigenetic mechanism involved in the occurrence and development of pancreatic cancer, which has the potential to diagnose of PDAC and is closely related to the prognosis.
RNA编辑是一种广泛认可的转录后机制，据报道其参与癌症的发生和发展，尤其是腺苷向肌苷的异常改变。然而，针对胰腺癌的研究较少。因此，我们旨在探索RNA编辑事件改变与胰腺导管腺癌（PDAC）发展之间的可能联系。
我们从41例原发性PDAC及其相邻正常组织的RNA和匹配的全基因组测序数据中，对全局A到I RNA编辑谱进行了表征。进行了以下分析：不同编辑水平和RNA表达分析、通路分析、基序分析、RNA二级结构分析、可变剪接事件分析和生存分析。还对单细胞RNA公共测序数据的RNA编辑进行了表征。
鉴定出大量编辑水平存在显著差异的适应性RNA编辑事件，这些事件主要受ADAR1调控。此外，肿瘤中的RNA编辑总体上具有更高的编辑水平和更丰富的编辑位点。筛选出140个基因，因为它们被鉴定出具有显著不同的RNA编辑事件，并且在肿瘤与匹配的正常样本之间的表达水平存在显著差异。进一步分析表明，在肿瘤特异性组中，它们主要富集于癌症相关信号通路，而在正常组织特异性组中，它们主要富集于胰腺分泌。同时，我们还在一系列癌症免疫基因中发现了正选择的差异编辑位点，包括EGF、IGF1R和PIK3CD。RNA编辑可能通过调节重要基因的可变剪接和RNA二级结构来参与PDAC的发病机制，进而进一步调节基因表达和蛋白质合成，包括RAB27B和CERS4。此外，单细胞测序结果表明，2型导管细胞对肿瘤中的RNA编辑事件贡献最大。
RNA编辑是一种参与胰腺癌发生和发展的表观遗传机制，具有诊断PDAC的潜力，且与预后密切相关。
