Transcriptome Sequencing of LYPLA1 Gene Overexpression and Interference

Previous studies have indicated that changes in LYPLA1 expression affect the proliferation and differentiation of fetal sheep myoblasts; however, the underlying molecular mechanisms remain unclear. This study examined transcriptional responses to LYPLA1 overexpression and knockdown in primary myoblasts derived from one Hu sheep fetus and explored the involvement of PI3K-Akt signaling in LYPLA1-associated proliferation. RNA sequencing showed that no differentially expressed genes remained significant after false discovery rate correction following LYPLA1 knockdown, whereas LYPLA1 overexpression yielded 362 significant genes, including 219 upregulated and 143 downregulated genes. Exploratory enrichment analysis of nominally significant candidate genes implicated extracellular and immune-related functions, steroid hormone biosynthesis, PPAR signaling, cytokine-cytokine receptor interaction, and PI3K-Akt signaling. Pharmacological inhibition with 0.5 μM PI3K/AKT-IN-1 partially attenuated the increases in EdU-positive cells and Cyclin D1 mRNA levels associated with LYPLA1 overexpression. These findings indicate that LYPLA1 overexpression is associated with broad transcriptional changes in ovine myoblasts and suggest that PI3K-Akt signaling contributes to the associated proliferative phenotype. However, the underlying mechanism requires further validation.