Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
University of Hawai'i Cancer Center, Honolulu, HI, 96813, USA.
Int J Biol Sci. 2017 Nov 1;13(11):1438-1449. doi: 10.7150/ijbs.20836. eCollection 2017.
Intronic miRNAs, residing in intronic regions of host genes, are thought to be co-transcribed from their host genes and present consistent expression patterns with host genes. Recent studies reported a few intronic miRNAs with discordant expression with their host genes. We therefore aimed to understand the expression pattern of intronic miRNAs and their host genes in hepatocellular carcinoma (HCC) and reveal possible associated molecular mechanisms. Our genome wide integration analysis of miRNA and mRNA transcriptomes, in three dataset from 550 patients with HCC, found that a large amount of miRNA-host gene pairs were discordantly expressed. Consistent results were also revealed in 775 breast cancer patients. Further, most of HCC-related intronic miRNAs were predicted to have distinct upstream regulators and independent proximal promoter signals from host genes. The discordant expression of representative pairs, miR-26s/CTDSPs, was validated experimentally. We have also identified the independent transcriptional start site, promoter signal, and transcriptional factor of miR-26b from its host gene. Collectively, discordant expression of intronic miRNAs and their host genes was relatively ubiquitous and the intronic miRNA "independent transcription" may partially contribute to such a phenotype.
内含子 miRNA 位于宿主基因的内含子区域，被认为是与其宿主基因共转录的，并且与宿主基因具有一致的表达模式。最近的研究报道了一些与宿主基因表达不一致的内含子 miRNA。因此，我们旨在了解肝细胞癌 (HCC) 中内含子 miRNA 及其宿主基因的表达模式，并揭示可能相关的分子机制。我们对来自 550 名 HCC 患者的三个数据集的 miRNA 和 mRNA 转录组进行了全基因组整合分析，发现大量 miRNA-宿主基因对表达不一致。在 775 名乳腺癌患者中也得到了一致的结果。此外，大多数 HCC 相关的内含子 miRNA 被预测具有与其宿主基因不同的上游调控因子和独立的近端启动子信号。代表性对 miR-26s/CTDSPs 的不一致表达通过实验得到了验证。我们还确定了 miR-26b 与其宿主基因的独立转录起始位点、启动子信号和转录因子。总的来说，内含子 miRNA 及其宿主基因的表达不一致是相当普遍的，内含子 miRNA 的“独立转录”可能部分导致了这种表型。
