Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Laboratory of Translational Medicine, Chinese PLA General Hospital, Beijing. 100853, China.
Biochim Biophys Acta Mol Cell Res. 2017 Oct;1864(10):1703-1713. doi: 10.1016/j.bbamcr.2017.06.003. Epub 2017 Jun 7.
Several studies have shown that long non-coding RNAs (lncRNAs) may play an essential role in Epithelial-Mesenchymal Transition (EMT), which is an important step in tumor metastasis; however, little is known about the global change of lncRNA transcriptome during EMT. To investigate how lncRNA transcriptome alterations contribute to EMT progression regulation, we deep-sequenced the whole-transcriptome of MCF10A as the cells underwent TGF-β-induced EMT.
Deep-sequencing results showed that the long RNA transcriptome of MCF10A had undergone global changes as early as 8h after treatment with TGF-β. The expression of 3403 known and novel lncRNAs, and 570 known and novel circRNAs were altered during EMT. To identify the key lncRNA-regulator, we constructed the co-expression network and found all junction nodes in the network are lncRNAs. One junction node, RP6-65G23.5, was further verified as a key regulator of EMT. Intriguingly, we identified 216 clusters containing lncRNAs which were located in "gene desert" regions. The expressions of all lncRNAs in these clusters changed concurrently during EMT, strongly suggesting that these clusters might play important roles in EMT. Our study reveals a global reprogramming of lncRNAs transcriptome during EMT and provides clues for the future study of the molecular mechanism of EMT.
几项研究表明,长非编码 RNA(lncRNA)可能在 EMT 中发挥重要作用,EMT 是肿瘤转移的重要步骤;然而,lncRNA 转录组在 EMT 过程中的整体变化知之甚少。为了研究 lncRNA 转录组的变化如何影响 EMT 进展的调控,我们对 MCF10A 细胞进行 TGF-β诱导的 EMT 时的整个转录组进行了深度测序。
深度测序结果表明,MCF10A 的长 RNA 转录组早在用 TGF-β处理 8 小时后就发生了全局变化。在 EMT 过程中,3403 个已知和新的 lncRNA 以及 570 个已知和新的 circRNA 的表达发生了改变。为了识别关键的 lncRNA 调节因子,我们构建了共表达网络,发现网络中的所有连接节点都是 lncRNA。一个连接节点 RP6-65G23.5 进一步被验证为 EMT 的关键调节因子。有趣的是,我们鉴定出 216 个包含位于“基因荒漠”区域的 lncRNA 的簇。这些簇中的所有 lncRNA 的表达在 EMT 过程中同时发生变化,强烈表明这些簇可能在 EMT 中发挥重要作用。我们的研究揭示了 EMT 过程中 lncRNA 转录组的全面重编程,并为 EMT 分子机制的未来研究提供了线索。