Fan Yixuan, Zhang Zhen, Deng Kaiping, Kang Ziqi, Guo Jinjing, Zhang Guomin, Zhang Yanli, Wang Feng
Jiangsu Livestock Embryo Engineering Laboratory, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Jiangsu Livestock Embryo Engineering Laboratory, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Int J Biol Macromol. 2023 Jan 31;226:730-745. doi: 10.1016/j.ijbiomac.2022.12.064. Epub 2022 Dec 13.
circRNAs have been found to be involved in the regulatory network of skeletal muscle development in studies. However, their precise functions and regulatory mechanisms remain unknown. The expression patterns and alterations of circRNAs in the longissimus dorsi muscle of two major developmental stages of goats (D75 fetus and D1 kid) were studied using high-throughput sequencing technology and bioinformatics tools in this study. In kid skeletal muscles, 831 differently expressed circRNAs were found, comprising 486 up-regulated circRNAs and 345 down-regulated circRNAs. In skeletal muscle, we focused on the highly expressed and variably expressed circUBE3A. CircUBE3A levels were discovered to be much higher in kid skeletal muscle and differentiated myoblasts. Knocking down circUBE3A resulted in a significant increase in cell proliferation and differentiation in goat myoblasts. CircUBE3A specifically binds to and inhibits miR-28-5p, boosting the expression of Hydroxyacyl Coenzyme A Dehydrogenase Beta (HADHB) and contributing to goat myoblast proliferation and differentiation, according to the mechanistic investigation. The above results indicated that circUBE3A could regulate HADHB expression by targeting miR-28-5p, consequently increasing goat myoblast proliferation and differentiation. Our findings offer fresh perspectives on goat breeding and growth regulation, as well as substantial theoretical basis.
在研究中发现环状RNA(circRNAs)参与骨骼肌发育的调控网络。然而,它们的确切功能和调控机制仍不清楚。本研究利用高通量测序技术和生物信息学工具,研究了山羊两个主要发育阶段(胎儿75天和出生1天的羔羊)背最长肌中circRNAs的表达模式和变化。在羔羊骨骼肌中,发现了831个差异表达的circRNAs,其中包括486个上调的circRNAs和345个下调的circRNAs。在骨骼肌中,我们聚焦于高表达和可变表达的circUBE3A。发现circUBE3A在羔羊骨骼肌和分化的成肌细胞中的水平要高得多。敲低circUBE3A导致山羊成肌细胞的细胞增殖和分化显著增加。根据机制研究,circUBE3A特异性结合并抑制miR-28-5p,促进羟酰基辅酶A脱氢酶β(HADHB)的表达,从而促进山羊成肌细胞的增殖和分化。上述结果表明,circUBE3A可通过靶向miR-28-5p调控HADHB的表达,进而增加山羊成肌细胞的增殖和分化。我们的研究结果为山羊育种和生长调控提供了新的视角,也提供了坚实的理论基础。