lncRNA AK159072 Promotes Myoblast Proliferation and Muscle Regeneration Through Activation of Akt/Foxo1 Pathway

Long non-coding RNAs (lncRNAs) are significant regulators of myoblast proliferation, migration and regeneration. In our previous research, we identified that lncRNA AK159072 was differentially expressed during myoblast development. In this study, we would like to explore the regulatory role and the mechanisms of AK159072 in proliferation. We discovered that AK159072 was increasingly expressed during myoblast proliferation and was located in both the nucleus and cytoplasm of proliferating C2C12 myoblasts. Overexpression of AK159072 promoted the expression of proliferation-related genes c-Myc, cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6 in C2C12 myoblasts. Additionally, the cell viability and EdU-positive cells were increased, while the wound size was decreased after overexpression AK159072. In contrast, cell proliferation was attenuated when AK159072 was successfully silenced. Furthermore, the cross sectional area (CSA) and proliferative markers were decreased after knockdown of AK159072 in the mouse hind leg muscles with CTX-induced injury in vivo, indicating that knockdown of AK159072 may delay muscle regeneration. The study further demonstrated that Akt/Foxo1 pathway mediated the effects of AK159072 overexpression and knockdown in myoblasts. Taken together, our results suggested that AK159072 may regulate myoblast proliferation and muscle regeneration via Akt/Foxo1 pathway. The study suggestd that modulating the expression of AK159072 could be a potential therapeutic strategy for muscle injuries, this could have significant clinical relevance for conditions such as muscular dystrophy, sarcopenia, and other muscle disorders.