基因下游 (DoG) 转录本是一类新兴的非编码 RNA。然而，DoG RNA 的产生是如何调节的以及主要癌症中是否存在 DoG RNA 特征的改变仍然很大程度上未知。在这里，通过对匹配的肿瘤和非肿瘤组织以及癌细胞系进行转录组分析，我们揭示了 DoG RNA 特征的全面目录。通过不同的证据，我们支持 DoG RNA 在致癌作用中的生物学重要性。首先，我们展示了肿瘤中 DoG RNA 的组织特异性和阶段特异性差异表达与配对的正常组织及其各自参与肿瘤促进与肿瘤抑制途径的宿主基因的差异。其次，我们发现差异性 DoG RNA 表达与患者生存率低相关。第三，我们确定 DoG RNA 诱导是用拓扑异构酶 I (TOP1) 毒物喜树碱处理结肠癌细胞并在 TOP1 耗尽后的结果。我们的结果证明了 DoG RNA 和 DoG RNA 的 TOP1 依赖性调节在癌症转录组多样化和调节中的重要性。

Downstream-of-gene (DoG) transcripts are an emerging class of noncoding RNAs. However, it remains largely unknown how DoG RNA production is regulated and whether alterations in DoG RNA signatures exist in major cancers. Here, through transcriptomic analyses of matched tumors and nonneoplastic tissues and cancer cell lines, we reveal a comprehensive catalog of DoG RNA signatures. Through separate lines of evidence, we support the biological importance of DoG RNAs in carcinogenesis. First, we show tissue-specific and stage-specific differential expression of DoG RNAs in tumors versus paired normal tissues with their respective host genes involved in tumor-promoting versus tumor-suppressor pathways. Second, we identify that differential DoG RNA expression is associated with poor patient survival. Third, we identify that DoG RNA induction is a consequence of treating colon cancer cells with the topoisomerase I (TOP1) poison camptothecin and following TOP1 depletion. Our results underlie the significance of DoG RNAs and TOP1-dependent regulation of DoG RNAs in diversifying and modulating the cancer transcriptome.