MiRNA-target interactions in osteogenic signaling pathways involving zinc and the metal regulatory element

The miRNA positions taken from microTSS supplementary data was batch converted to hg38. Those miRNAs were then put into a query for TarBase validated target interactions with genes found in the KEGG pathways TGF-beta, MAPK, and Wnt to find which of these miRNAs are involved with osteogenesis processes. The TSSs for 86 pre-miRNA genes were predicted by the microTSS algorithm; 44 of these pre-miRNAs contain an MRE within the range specified, without interruption between the MRE motif and the MIR gene TSS by the presence of another gene. These 44 pre-miRNAs equate to 73 mature miRNAs. Within the TGF-β, MAPK, and Wnt signaling pathways, 65 of the 73 mature miRNAs have Tarbase-verified MTIs (hereafter called “verified MTIs”) with 241 genes. Of the 460 genes in these three signaling pathways, 413 have an MRE in the range specified. Of those 413 genes, 213 have verified MTIs with 64 mature miRNAs which also have MREs. The TGF-β pathway contained MTIs consisting of 39 miRNAs/44 genes, the MAPK pathway contained MTIs consisting of 57 miRNAs/130 genes, and the Wnt pathway contained MTIs consisting of 43 miRNAs/61 genes. MAPK1 exhibited 10 MTIs, the most verified MTIs in the TGF-β and MAPK signaling pathways. CCND2 exhibited 9 MTIs, the most verified MTIs in the Wnt signaling pathway. Hsa-miR-124-3p targeted the most genes in the TGF-β (12 genes) and MAPK (32 genes) signaling pathways. Hsa-miR-20b-5p targeted the most genes, 12, in the Wnt signaling pathway.

本研究中提取自microTSS补充数据集的微小RNA（microRNA, miRNA）位点经批次转换至人类参考基因组hg38版本。随后以这些miRNA为查询对象，在TarBase数据库中检索其与KEGG通路转化生长因子β（TGF-β）、丝裂原活化蛋白激酶（MAPK）及Wnt通路所覆盖基因的经验证靶标相互作用，以筛选参与成骨过程的miRNA。
microTSS算法共预测得到86个前体微小RNA（pre-miRNA）基因的转录起始位点（TSS）；其中44个pre-miRNA在指定区间内包含miRNA应答元件（MRE），且该元件与miRNA基因TSS之间未因其他基因的存在而产生间隔中断。上述44个pre-miRNA对应73个成熟miRNA。
在TGF-β、MAPK及Wnt信号通路中，73个成熟miRNA中有65个与241个基因存在经TarBase验证的靶标相互作用（以下简称“验证型MTIs”）。上述三条信号通路共包含460个基因，其中413个在指定区间内携带MRE；在这413个基因中，有213个与64个同样携带MRE的成熟miRNA存在经验证的靶标相互作用。
其中，TGF-β通路的验证型MTIs涉及39个miRNA与44个基因，MAPK通路涉及57个miRNA与130个基因，Wnt通路涉及43个miRNA与61个基因。丝裂原活化蛋白激酶1（MAPK1）的验证型MTIs数量达10个，为TGF-β与MAPK信号通路中最多。细胞周期蛋白D2（CCND2）的验证型MTIs数量达9个，为Wnt信号通路中最多。hsa-miR-124-3p在TGF-β通路（靶向12个基因）及MAPK通路（靶向32个基因）中靶向的基因数量最多。hsa-miR-20b-5p在Wnt信号通路中靶向的基因数量最多，共计12个。