Jiang Leiming, Chen Qiuyang, Bei Mingrong, Shao Mengting, Xu Jianzhen
Computational Systems Biology Laboratory, Department of Bioinformatics, Shantou University Medical College (SUMC), 515041 Shantou, China.
Comput Struct Biotechnol J. 2021 Sep 17;19:5235-5245. doi: 10.1016/j.csbj.2021.09.019. eCollection 2021.
The interactions among non-coding RNA (ncRNA) and RNA binding protein (RBP) are increasingly recognized as one of basic mechanisms in gene regulation, and play a crucial role in cancer progressions. However, the current understanding of this regulation network, especially its dynamic spectrum according to the differentially expressed nodes ( ncRNAs and RBP) is limited. Utilizing transcriptomics and interactomics resources, dysregulated RBP-ncRNA circuits (RNCs) are systematically dissected across 14 tumor types. We found these aberrant RNCs are robust and enriched with cancer-associated ncRNAs, RBPs and drug targets. Notably, the nodes in altered RNCs can jointly predict the clinical outcome while the individual node can't, underscoring RNCs can serve as prognostic biomarkers. We identified 30 pan-cancer RNCs dysregulated at least in six tumor types. Pan-cancer RNC analysis can reveal novel mechanism of action (MOA) and repurpose for existing drugs. Importantly, our experiments elucidated the novel role of hsa-miR-224-5p, a member of the pan-cancer RNC hsa-miR-224-5p_MAGI2-AS3_MBNL2, in EMT program. Our analysis highlights the potential utilities of RNCs in elucidating ncRNA function in cancer, associating with clinical outcomes and discovering novel drug targets or MOA.
非编码RNA（ncRNA）与RNA结合蛋白（RBP）之间的相互作用日益被认为是基因调控的基本机制之一，并在癌症进展中发挥关键作用。然而，目前对这一调控网络的理解，尤其是根据差异表达节点（ncRNAs和RBP）的动态图谱，仍然有限。利用转录组学和相互作用组学资源，我们在14种肿瘤类型中系统地剖析了失调的RBP-ncRNA回路（RNCs）。我们发现这些异常的RNCs很稳定，并且富含癌症相关的ncRNAs、RBPs和药物靶点。值得注意的是，RNCs中改变的节点能够共同预测临床结果，而单个节点则不能，这突出表明RNCs可作为预后生物标志物。我们鉴定出至少在六种肿瘤类型中失调的30个泛癌RNCs。泛癌RNC分析能够揭示新的作用机制（MOA）并重新利用现有药物。重要的是，我们的实验阐明了泛癌RNC hsa-miR-224-5p_MAGI2-AS3_MBNL2的成员hsa-miR-224-5p在EMT程序中的新作用。我们的分析突出了RNCs在阐明ncRNA在癌症中的功能、与临床结果相关联以及发现新的药物靶点或MOA方面的潜在用途。
