Qiu Jiaying, Wang Lingbin, Wang Ye, Zhang Qiuyu, Ma Wenjing, Fang Qingqing, Sun Hualin, Ding Fei
School of Biology and Basic Medical Sciences, Medical College of Soochow University, Suzhou 215123, China.
Laboratory of Neuroregeneration, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
J Thorac Dis. 2018 Nov;10(11):6238-6246. doi: 10.21037/jtd.2018.10.88.
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.
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.
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).
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.
糖皮质激素，包括地塞米松（Dex），是肾上腺分泌的皮质类固醇，用作强效抗炎、抗休克和免疫抑制剂。Dex常用于恶性肿瘤患者，如肺癌患者。然而，高剂量Dex的使用会导致骨骼肌严重萎缩，这种骨骼肌萎缩的潜在机制仍不清楚。骨骼肌中丰富的微小RNA，如miR-351，在减轻肌肉萎缩过程的调节中起重要作用。
通过实时PCR和蛋白质免疫印迹法测定肿瘤坏死因子受体相关因子6（TRAF6）、肌肉环指蛋白1（MuRF1）、肌肉萎缩F盒蛋白（MAFbx）的mRNA和蛋白表达，同时通过实时PCR检测miR-351的表达。用miR-351模拟物、阴性对照或miR-351抑制剂转染肌管。测量C2C12肌管直径。
在Dex诱导的C2C12肌管萎缩中，微小RNA351（miR-351）水平显著降低，肿瘤坏死因子（TNF）受体相关因子6（TRAF6）的mRNA和蛋白水平升高。miR-351直接与TRAF6的3'非翻译区（3'UTR）相互作用。有趣的是，给予miR-351显著抑制了Dex处理诱导的C2C12肌管直径减小，并降低了TRAF6、肌肉环指蛋白1（MuRF1）和肌肉萎缩F盒蛋白（MAFbx）的水平。
miR-351通过抑制TRAF6表达以及E3泛素连接酶MuRF1和MAFbx来对抗Dex诱导的C2C12肌管萎缩。miR-351可能是开发骨骼肌萎缩新策略的潜在靶点。
