Jiaying Qiu1, Lingbin Wang2, Ye Wang3, Qiuyu Zhang2, Wenjing Ma2, Qingqing Fang2, Hualin Sun2, Fei Ding1,2. 1. School of Biology and Basic Medical Sciences, Medical College of Soochow University, Suzhou 215123, China. 2. Laboratory of Neuroregeneration, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. 3. School of Medicine, Nantong University, Nantong 226001, China.
Abstract
BACKGROUND: Glucocorticoids, including dexamethasone (Dex), are corticosteroids secreted by the adrenal gland, which are used as potent anti-inflammatory, anti-shock, and immunosuppressive agents. Dex is commonly used in patients with malignant tumors, such lung cancer. However, administration of high-dose Dex induces severe atrophy of the skeletal muscle, and the underlying mechanisms of this skeletal muscle atrophy remain unclear. Abundant miRNAs of skeletal muscle, such as miR-351, play an important role in the regulation of extenuating the process of muscle atrophy. METHODS: The mRNA and protein expression of TRAF6, MuRF1, MAFbx was determined by real-time PCR and western blot, while the expression of miR-351 was detected by real-time PCR. The myotubes were transfected with miR-351 mimic, negative control, or miR-351 inhibitor. The C2C12 myotubes diameter was measured. RESULTS: MicroRNA351 (miR-351) level was markedly reduced and the mRNA and protein levels of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) were increased in Dex-induced C2C12 myotube atrophy. miR-351 directly interacted with the 3'-untranslated region (3'UTR) of TRAF6. Interestingly, miR-351 administration notably inhibited the reduction of the C2C12 myotube diameter induced by Dex treatment and reduced the levels of TRAF6, muscle-RING-finger protein-1 (MuRF1), and muscle atrophy F-box (MAFbx). CONCLUSIONS: miR-351 counteracts Dex-induced C2C12 myotube atrophy by repressing the TRAF6 expression as well as E3 ubiquitin ligase MuRF1 and MAFbx. miR-351 maybe a potential target for development of a new strategy for skeletal muscle atrophy.
BACKGROUND: Glucocorticoids, including dexamethasone (Dex), are corticosteroids secreted by the adrenal gland, which are used as potent anti-inflammatory, anti-shock, and immunosuppressive agents. Dex is commonly used in patients with malignant tumors, such lung cancer. However, administration of high-dose Dex induces severe atrophy of the skeletal muscle, and the underlying mechanisms of this skeletal muscle atrophy remain unclear. Abundant miRNAs of skeletal muscle, such as miR-351, play an important role in the regulation of extenuating the process of muscle atrophy. METHODS: The mRNA and protein expression of TRAF6, MuRF1, MAFbx was determined by real-time PCR and western blot, while the expression of miR-351 was detected by real-time PCR. The myotubes were transfected with miR-351 mimic, negative control, or miR-351 inhibitor. The C2C12 myotubes diameter was measured. RESULTS: MicroRNA351 (miR-351) level was markedly reduced and the mRNA and protein levels of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) were increased in Dex-induced C2C12 myotube atrophy. miR-351 directly interacted with the 3'-untranslated region (3'UTR) of TRAF6. Interestingly, miR-351 administration notably inhibited the reduction of the C2C12 myotube diameter induced by Dex treatment and reduced the levels of TRAF6, muscle-RING-finger protein-1 (MuRF1), and muscle atrophy F-box (MAFbx). CONCLUSIONS: miR-351 counteracts Dex-induced C2C12 myotube atrophy by repressing the TRAF6 expression as well as E3 ubiquitin ligase MuRF1 and MAFbx. miR-351 maybe a potential target for development of a new strategy for skeletal muscle atrophy.
Authors: Megan E Rosa-Caldwell; Marie Mortreux; Ursula B Kaiser; Dong-Min Sung; Mary L Bouxsein; Kirsten R Dunlap; Nicholas P Greene; Seward B Rutkove Journal: Exp Physiol Date: 2021-10-18 Impact factor: 2.858