Skeletal muscle is the largest motor and metabolic organ of the body, which has a robust capacity for regeneration following injury or disease. Delayed regeneration after skeletal muscle injury reduces muscle contractility and leads to dysfunction of innervation. Therefore, identifying the regulation components in skeletal muscle regeneration and determining their molecular mechanisms are important to discover novel therapeutic markers for muscular diseases. Long non-coding RNA (LncRNA) has been implicated in skeletal muscle regeneration. Recent developed singlecell RNA sequencing (scRNA-seq) provides a higher resolution of cellular differences than bulk RNA-seq. Here, we reanalyzed single-cell transcriptomes data of skeletal muscle regeneration and identified lncRNA maternally expressed gene 3 (lncRNA-MEG3) was highly expressed in muscle satellite cells (MuSCs). Further study showed that lncRNA-MEG3 regulates skeletal muscle regeneration via sponging miR-133a-3p to regulate proline-rich transmembrane protein 2 (PRRT2) expression level. These results suggested that lncRNA-MEG3 might be a potential target for skeletal muscle diseases.