Myogenic differentiation 1 (MyoD1) is a transcription factor that promotes expression of muscle-specific genes. MyoD1 is expressed at significantly lower levels in gastric cancer (GC) tissues and cells, and it induces apoptosis in GC cells. However, functions for MyoD1 in GC cell migration and gene expression have not been documented. We show that knockdown of MyoD1 promoted migration and invasion of GC cells, whereas MyoD1 overexpression suppressed migration and invasion. We performed chromatin immunoprecipitation (ChIP)-sequencing to identify MyoD1 target genes in MKN-45 cells. The 2-kb upstream regions (Up2k) of the transcription start sites of 57 genes were probably bound by MyoD1. Six of these genes function in signaling pathways such as synthesis of glycosphingolipid biosynthesis—lacto and neolacto series. MyoD1 inhibited transcription of fucosyltransferase IV (FUT4) by binding directly to the FUT4 F3; this finding was validated by ChIP-quantitative PCR and a luciferase reporter assay. Ulex europaeus agglutinin I, which binds Fucα1-2Galβ1-4GlcNAc, and Lewis antigens showed decreased binding to the plasma membrane of cells that overexpressed MyoD1. Knockdown of FUT4 mimicked MyoD1 overexpression by suppressing GC cell migration and invasion; this result implied that MyoD1 suppressed cell migration and invasion via inhibiting the FUT4/matrix metallopeptidase signaling pathway. In summary, this study demonstrated that MyoD1 suppresses migration and invasion of GC cells by directly binding to the F3 region in the FUT4 Up2k and inhibiting FUT4/type II Lewis antigen expression.

肌源性分化 1 (MyoD1) 是一种促进肌肉特异性基因表达的转录因子。MyoD1 在胃癌 (GC) 组织和细胞中的表达水平显着降低，并诱导 GC 细胞凋亡。然而，尚未记录 MyoD1 在 GC 细胞迁移和基因表达中的功能。我们表明，MyoD1 的敲低促进了 GC 细胞的迁移和侵袭，而 MyoD1 过表达抑制了迁移和侵袭。我们进行染色质免疫沉淀 (ChIP) 测序以鉴定 MKN-45 细胞中的 MyoD1 靶基因。57 个基因转录起始位点的 2-kb 上游区域 (Up2k) 可能与 MyoD1 结合。这些基因中有六个在信号通路中起作用，例如鞘糖脂生物合成的合成——lacto 和 neolacto 系列。FUT4 F3; 这一发现得到了 ChIP 定量 PCR 和荧光素酶报告基因检测的验证。结合 Fucα1-2Galβ1-4GlcNAc 和 Lewis 抗原的欧洲榆树凝集素 I 显示与过表达 MyoD1 的细胞质膜的结合降低。通过抑制 GC 细胞迁移和侵袭，FUT4 的敲低模拟了 MyoD1 的过度表达；该结果表明，MyoD1 通过抑制 FUT4/基质金属肽酶信号通路来抑制细胞迁移和侵袭。总之，该研究表明，MyoD1 通过直接结合FUT4 Up2k 中的 F3 区域并抑制 FUT4/II 型 Lewis 抗原表达来抑制GC 细胞的迁移和侵袭。