SOX6 AU controls myogenesis by cis-modulation of SOX6 in cattle

Epigenetics. 2024 Dec;19(1):2341578. doi: 10.1080/15592294.2024.2341578. Epub 2024 Apr 14.

Abstract

Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of skeletal muscle development through multiple mechanisms. The present study revealed that the lncRNA SOX6 AU (SRY-box transcription factor 6 antisense upstream) is reverse transcribed from upstream of the bovine sex-determining region Y (SRY)-related high-mobility-group box 6 (SOX6) gene. SOX6 AU was significantly differentially expressed in muscle tissue among different developmental stages in Xianan cattle. Subsequently, knockdown and overexpression experiments discovered that SOX6 AU promoted primary skeletal muscle cells proliferation, apoptosis, and differentiation in bovine. The overexpression of SOX6 AU in bovine primary skeletal muscle cells resulted in 483 differentially expressed genes (DEGs), including 224 upregulated DEGs and 259 downregulated DEGs. GO functional annotation analysis showed that muscle development-related biological processes such as muscle structure development and muscle cell proliferation were significantly enriched. KEGG pathway analysis revealed that the PI3K/AKT and MAPK signaling pathways were important pathways for DEG enrichment. Notably, we found that SOX6 AU inhibited the mRNA and protein expression levels of the SOX6 gene. Moreover, knockdown of the SOX6 gene promoted the proliferation and apoptosis of bovine primary skeletal muscle cells. Finally, we showed that SOX6 AU promoted the proliferation and apoptosis of bovine primary skeletal muscle cells by cis-modulation of SOX6 in cattle. This work illustrates our discovery of the molecular mechanisms underlying the regulation of SOX6 AU in the development of beef.

Keywords: Bovine primary skeletal muscle cells; SOX6; SOX6 AU; apoptosis; cis-modulation; proliferation.

MeSH terms

  • Animals
  • Apoptosis
  • Cattle
  • Cell Differentiation
  • DNA Methylation
  • Muscle Development / genetics
  • Phosphatidylinositol 3-Kinases* / genetics
  • RNA, Long Noncoding*

Substances

  • Phosphatidylinositol 3-Kinases
  • RNA, Long Noncoding

Grants and funding

This research was funded by the National Natural Science Foundation of China (No. 32002168), the Key Scientific and Technological Project of Henan Province Department of China (222102110152), and Special Fund for the Henan Agriculture Research System (No. HARS-22-13-G1).