Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, Korea.
GENINUS Inc., Seoul, Korea.
FASEB J. 2021 Apr;35(4):e21482. doi: 10.1096/fj.202002297RRR.
Antisense transcription occurs widely more expected than when it was first identified in bacteria in the 1980s. However, the functional relevance of antisense transcripts in transcription remains controversial. Here, we investigated the putative role of antisense transcripts in regulating their corresponding sense transcripts by analyzing changes in correlative relationships between sense-antisense pairs under tumor and normal conditions. A total of 3469 sense-antisense gene pairs (SAGPs) downloaded from BioMart mapped to a list of sense and antisense genes in RNA-seq data derived from 80 paired colorectal cancer (CRC) samples were analyzed. As a result, cancer-related genes were significantly enriched in the significantly correlated SAGPs (SCPs). Differentially expressed genes estimated between normal and tumor conditions were also significantly more enriched in SCPs than in non-SCPs. Interestingly, using differential correlation analysis, we found that tumor samples had a significantly larger density of genes with higher correlation coefficients than normal samples, as verified by various cancer transcriptomes from The Cancer Genome Atlas (TCGA). Moreover, we found that the magnitude of the correlation between SAGPs could distinguish poor prognostic CRCs from good prognostic CRCs, showing that correlation coefficients between the SAGPs of CRCs with a poor prognosis were significantly stronger than CRCs with a good prognosis. Consistent with this finding, the Cox proportion hazards model showed that the survival rates were significantly different between patients with high and low expression of genes in the SCPs. All these results strongly support the idea that antisense transcripts are important regulators of their corresponding sense transcripts.
反义转录的发生范围比 20 世纪 80 年代首次在细菌中发现时更为广泛。然而，反义转录本在转录中的功能相关性仍然存在争议。在这里，我们通过分析肿瘤和正常条件下相关对之间相关性的变化，研究了反义转录本通过调节其相应的有义转录本的可能作用。从 BioMart 下载的总共 3469 个有义-反义基因对（SAGP）映射到从 80 对结直肠肿瘤（CRC）样本的 RNA-seq 数据中获得的有义和反义基因列表，分析了这些 SAGP。结果表明，癌症相关基因在显著相关的 SAGP（SCP）中显著富集。在正常和肿瘤条件下估计的差异表达基因在 SCP 中也比在非 SCP 中更显著富集。有趣的是，使用差异相关分析，我们发现肿瘤样本的高相关系数基因密度明显高于正常样本，这在来自癌症基因组图谱（TCGA）的各种癌症转录组中得到了验证。此外，我们发现 SAGP 之间的相关性大小可以区分预后不良的 CRC 和预后良好的 CRC，表明预后不良的 CRC 的 SAGP 之间的相关性系数明显强于预后良好的 CRC。与此发现一致，Cox 比例风险模型显示，高表达和低表达 SCP 基因的患者的生存率存在显著差异。所有这些结果都强烈支持反义转录本是其相应有义转录本的重要调节因子的观点。
