PDF(Pubmed)
Abstract：
Myogenic differentiation (MyoD) 1, which is known as a pivotal transcription factor during myogenesis, has been proven dysregulated in several cancers. However, litter is known about the precise role and downstream genes of MyoD1 in gastric cancer (GC) cells. Here, we report that MyoD1 is lowly expressed in primary GC tissues and cells. In our experiments, overexpression of MyoD1 inhibited cell proliferation. Downstream genes of MyoD1 regulation were investigated using RNA-Seq. As a result, 138 up-regulated genes and 20 down-regulated genes and 27 up-regulated lncRNAs and 20 down-regulated lncRNAs were identified in MyoD1 overexpressed MKN-45 cells, which participated in epithelial cell signaling in Helicobacter pylori infection, glycosaminoglycan biosynthesis (keratan sulfate), notch signaling pathway, and others. Among these genes, BIK was directly regulated by MyoD1 in GC cells and inhibited cancer cell proliferation. The BIK knockdown rescued the effects of MyoD1 overexpression on GC cells. In conclusion, MyoD1 inhibited cell proliferation via 158 genes and 47 lncRNAs downstream directly or indirectly that participated in multiple signaling pathways in GC, and among these, MyoD1 promotes BIK transcription by binding to its promoter, then promotes BIK-Bcl2-caspase 3 axis and regulates GC cell apoptosis.
摘要：
肌源性分化（MyoD）1，它被认为是肌形成过程中的关键转录因子，已被证明在几种癌症中失调。然而,关于MyoD1在胃癌（GC）细胞中的确切作用和下游基因是已知的。这里,我们报道MyoD1在原代GC组织和细胞中低表达。在我们的实验中,MyoD1的过表达抑制细胞增殖。使用RNA-Seq研究MyoD1调节的下游基因。因此,在MyoD1过表达的MKN-45细胞中鉴定出138个上调基因和20个下调基因以及27个上调lncRNAs和20个下调lncRNAs,参与了幽门螺杆菌感染的上皮细胞信号传导，糖胺聚糖生物合成（硫酸角质素），Notch信号通路,和其他人。在这些基因中,BIK在GC细胞中直接受MyoD1调节并抑制癌细胞增殖。BIK敲低挽救了MyoD1过表达对GC细胞的影响。总之,MyoD1通过158个基因和47个直接或间接下游的lncRNAs抑制细胞增殖，参与GC的多个信号通路，其中，MyoD1通过与其启动子结合促进BIK转录,然后促进BIK-Bcl2-caspase3轴并调节GC细胞凋亡。
