TY - JOUR AB - Skeletal muscle atrophy is a common feature of patients suffering with chronic infection and other systemic diseases, including acquired immunodeficiency syndrome, chronic kidney disease and cancer. Therefore, understanding the molecular basis of muscle loss is of importance. The majority of members of the forkhead box O (FoxO) family can induce skeletal muscle atrophy; however, the effect of FoxO6 on skeletal muscle is not completely understood. The present study investigated the role of FoxO6 in vitro and in vivo. Compared with the small interfering RNA (si)‑negative control (NC) group, C2C12 cell proliferation (Cell Counting Kit‑8 assay), myotube differentiation and myotube production were significantly decreased by FoxO6 knockdown, which was different from the known functions of other FoxO members. The immunofluorescence assay results demonstrated that si‑FoxO6 clearly downregulated the expression levels of myosin heavy chain (MyHC) in C2C12 myotubes compared with si‑NC. The western blotting results indicated that compared with the si‑NC group, FoxO6 knockdown induced C2C12 myotube atrophy by notably downregulating myoblast determination protein 1 (MyoD), mTOR and MyHC expression levels, and by markedly upregulating ubiquitin ligase (atrogin1) and muscle RING‑finger protein‑1 (MURF1) expression levels. Similarly, in an in vitro model of TNF‑α‑induced myotube atrophy, the western blotting results indicated that FoxO6 expression levels were decreased, whereas atrogin1, MURF1, FoxO1 and FoxO3a expression levels were increased compared with the control group. Therefore, the results indicated that, unlike FoxO1 or FoxO3a, FoxO6 maintained C2C12 myotubes and protected against atrophy. Consistent with the in vitro data, similar results were observed in vivo. Collectively, the results of the present study suggested that FoxO6 served a critical role in muscle cell metabolism in vitro and in vivo, and might serve as a promising therapeutic target for ameliorating skeletal muscle atrophy. AD - Department of Endocrinology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, P.R. China Department of Infection Disease, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610041, P.R. China Department of General Surgery, Chengdu Fifth People's Hospital, The Fifth People's Hospital Affiliated with Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611130, P.R. China AU - Zhang,Lei AU - Zhang,Yiyi AU - Zhou,Min AU - Wang,Shuang AU - Li,Tiane AU - Hu,Zhangyong AU - Jin,Chengwu DA - 2021/07/01 DO - 10.3892/ijmm.2021.4976 IS - 1 JO - Int J Mol Med KW - skeletal muscle atrophy forkhead box O6 C2C12 atrogin1 muscle RING‑finger protein‑1 PY - 2021 SN - 1107-3756 1791-244X SP - 143 ST - Role and mechanism underlying FoxO6 in skeletal muscle in vitro and in vivo T2 - International Journal of Molecular Medicine TI - Role and mechanism underlying FoxO6 in skeletal muscle in vitro and in vivo UR - https://doi.org/10.3892/ijmm.2021.4976 VL - 48 ER -