Adequate zinc nutriture is necessary for normal bone growth and development, though the precise mechanisms for zinc-mediated bone growth remain poorly defined. A key transcription factor activated by zinc is metal response element-binding transcription factor 1 (MTF-1), which binds to the metal regulatory element (MRE). We hypothesize that MREs will be found upstream of miRNA genes as well as miRNA target genes in the following bone growth and development signaling pathways: TGF-β, MAPK, and Wnt. A Bioconductor-based workflow in R was designed to identify interactions between MREs, miRNAs, and target genes. MRE sequences were found upstream from 64 mature miRNAs that interact with 213 genes which have MRE sequences in their own promoter regions. MAPK1 exhibited the most miRNA-target interactions (MTIs) in the TGF-β and MAPK signaling pathways; CCND2 exhibited the most interactions in the Wnt signaling pathway. Hsa-miR-124-3p exhibited the most MTIs in the TGF-β and MAPK signaling pathways; hsa-miR-20b-5p exhibited the most MTIs in the Wnt signaling pathway. MYC and hsa-miR-34a-5p were shared between all three signaling pathways, also forming an MTI unit. JUN exhibited the most protein-protein interactions, followed by MAPK8. These in silico data support the hypothesis that intracellular zinc status plays a role in osteogenesis through the transcriptional regulation of miRNA genes via the zinc/MTF-1/MRE complex.

中文翻译：

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通过金属调节元件，涉及锌的成骨信号传导途径中的MiRNA-靶标相互作用。

尽管锌介导的骨骼生长的精确机制仍然不清楚，但是适当的锌营养对于正常的骨骼生长和发育是必需的。锌激活的关键转录因子是金属响应元件结合转录因子1（MTF-1），它与金属调节元件（MRE）结合。我们假设MREs将在以下骨骼生长和发育信号通路中的miRNA基因以及miRNA靶基因的上游发现：TGF-β，MAPK和Wnt。R中基于生物导体的工作流程旨在识别MRE，miRNA和靶基因之间的相互作用。在与213个基因相互作用的64个成熟miRNA的上游发现了MRE序列，这些基因在其自身的启动子区域具有MRE序列。MAPK1在TGF-β和MAPK信号通路中表现出最多的miRNA-靶标相互作用（MTI）。CCND2在Wnt信号通路中表现出最多的相互作用。Hsa-miR-124-3p在TGF-β和MAPK信号通路中表现出最多的MTIs。hsa-miR-20b-5p在Wnt信号通路中表现出最多的MTI。MYC和hsa-miR-34a-5p在所有三个信号通路之间共享，也形成了MTI单元。JUN表现出最多的蛋白质-蛋白质相互作用，其次是MAPK8。这些计算机数据支持以下假设：细胞内锌状态通过经由锌/ MTF-1 / MRE复合体的miRNA基因的转录调控在成骨中起作用。MYC和hsa-miR-34a-5p在所有三个信号通路之间共享，也形成了MTI单元。JUN表现出最多的蛋白质-蛋白质相互作用，其次是MAPK8。这些计算机模拟数据支持以下假设：细胞内锌状态通过经由锌/ MTF-1 / MRE复合体的miRNA基因的转录调控在成骨中起作用。MYC和hsa-miR-34a-5p在所有三个信号通路之间共享，也形成了MTI单元。JUN表现出最多的蛋白质-蛋白质相互作用，其次是MAPK8。这些计算机数据支持以下假设：细胞内锌状态通过经由锌/ MTF-1 / MRE复合体的miRNA基因的转录调控在成骨中起作用。