Liu Quan, Zhou Honghong, Fu Chong, Han Min, Xie Su, Li Mengxun, Li Changchun
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education and Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education and Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China.
Int J Biol Macromol. 2025 May;308(Pt 4):142675. doi: 10.1016/j.ijbiomac.2025.142675. Epub 2025 Mar 29.
Skeletal muscle satellite cell proliferation and differentiation are important stages in skeletal muscle development, and long non-coding RNAs (lncRNAs) play important roles in both stages. We previously determined the basal functions of lncRNA H19 (H19) and the drebrin 1 (DBN1) gene in porcine skeletal muscle satellite cells (PSCs). However, the mechanisms for H19 and DBN1 regulation of the proliferation and differentiation of PSCs are still unclear. In this study, double luciferase report and pull down results confirmed H19 upregulates DBN1 expression by acting as a miR-935/miR-296-5p decoy. The western blotting results showed upregulated DBN expression activates the p38 mitogen-activated protein kinase (MAPK) pathway to inhibit PSC proliferation and promote differentiation. Moreover, ChIP results showed H19 transcription is regulated by the upstream transcription factor myc-associated zinc finger protein (MAZ). In conclusion, we resolved the mechanism for H19 regulation of proliferation and differentiation of PSCs, contributing to a deeper understanding of the epigenetic regulation of skeletal muscle development and will accelerate advancements in animal genetic improvement.
骨骼肌卫星细胞的增殖和分化是骨骼肌发育的重要阶段，长链非编码RNA（lncRNA）在这两个阶段均发挥重要作用。我们之前已确定lncRNA H19（H19）和 drebrin 1（DBN1）基因在猪骨骼肌卫星细胞（PSC）中的基础功能。然而，H19和DBN1调控PSC增殖和分化的机制仍不清楚。在本研究中，双荧光素酶报告和下拉结果证实H19通过作为miR - 935/miR - 296 - 5p的诱饵上调DBN1表达。蛋白质免疫印迹结果显示上调的DBN表达激活p38丝裂原活化蛋白激酶（MAPK）途径以抑制PSC增殖并促进分化。此外，染色质免疫沉淀结果显示H19转录受上游转录因子 myc相关锌指蛋白（MAZ）调控。总之，我们解析了H19调控PSC增殖和分化的机制，有助于更深入地了解骨骼肌发育的表观遗传调控，并将加速动物遗传改良的进展。
