Marek's disease (MD), induced by Marek's disease virus (MDV), is a lymphotropic neoplastic disease and causes huge economic losses to the poultry industry. Non-coding RNAs (ncRNAs) play important regulatory roles in disease pathogenesis. To investigate host circular RNA (circRNA) and microRNA (miRNA) expression profile, RNA sequencing was performed in tumourous spleens (TS), spleens from the survivors (SS) without any lesion after MDV infection, and non-infected chicken spleens (NS). A total of 2,169 circRNAs were identified and more than 80% of circRNAs were derived from exon. The flanking introns of 1,744 exonic circRNAs possessed 579 reverse complementary matches (RCMs), which mainly overlapped with chicken repeat 1 family (CR1F). It suggested that CR1F mediated the cyclization of exons by intron pairing. Out of 2,169 circRNAs, 113 were differentially expressed circRNAs (DECs). The Q-PCR and Rnase R digestion experiments showed circRNA possessed high stability compared with their linear RNAs. Integrated with previous transcriptome data, we profiled regulatory networks of circRNA/long non-coding RNA (lncRNA)-miRNA-mRNA. Extensive competing endogenous RNA (ceRNA) networks were predicted to be involved in MD tumourigenesis. Interestingly, circZMYM3, an intronic circRNA, interacted with seven miRNAs which targeted some immune genes, such as SWAP70 and CCL4. Gga-miR-155 not only interacted with circGTDC1 and circMYO1B, but also targeted immune-related genes, such as GATA4, which indicated the roles of non-coding RNAs played to mediate immune responsive genes. Collectively, this is the first study that integrated RNA expression profiles in MD model. Our results provided comprehensive interactions of ncRNAs and mRNA in MD tumourigenesis.

中文翻译：

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对参与鸡马立克氏病肿瘤发生的环状 RNA 进行全基因组分析。


马立克氏病(MD)是由马立克氏病病毒(MDV)引起的一种淋巴肿瘤性疾病，给养禽业造成巨大的经济损失。非编码 RNA (ncRNA) 在疾病发病机制中发挥重要的调节作用。为了研究宿主环状 RNA (circRNA) 和 microRNA (miRNA) 表达谱，对肿瘤脾脏 (TS)、MDV 感染后无任何病变的幸存者脾脏 (SS) 和未感染鸡脾脏 (NS) 进行了 RNA 测序。总共鉴定出 2,169 个 circRNA，其中超过 80% 的 circRNA 来自外显子。 1,744个外显子circRNA的侧翼内含子拥有579个反向互补匹配（RCM），主要与鸡重复1家族（CR1F）重叠。这表明CR1F通过内含子配对介导外显子环化。在 2,169 个 circRNA 中，有 113 个是差异表达的 circRNA (DEC)。 Q-PCR和Rnase R消化实验表明，与线性RNA相比，circRNA具有较高的稳定性。结合之前的转录组数据，我们分析了 circRNA/长非编码 RNA (lncRNA)-miRNA-mRNA 的调控网络。据预测，广泛的竞争性内源性 RNA (ceRNA) 网络参与 MD 肿瘤发生。有趣的是，circZMYM3（一种内含子 circRNA）与 7 个针对某些免疫基因（例如 SWAP70 和 CCL4）的 miRNA 相互作用。 Gga-miR-155不仅与circGTDC1和circMYO1B相互作用，而且还靶向免疫相关基因，例如GATA4，这表明非编码RNA在介导免疫应答基因中发挥着作用。总的来说，这是第一个将 RNA 表达谱整合到 MD 模型中的研究。我们的结果提供了 ncRNA 和 mRNA 在 MD 肿瘤发生中的全面相互作用。