Abstract：
Cancer-derived exosomes are involved in the development of cancer cachexia. Carnosol, which exhibited ameliorating effects on cancer cachexia of C26 tumour-bearing mice in our previous study, alleviated atrophy of C2C12 myotubes induced by exosomes of C26 tumour cells in the present study. MiR-183-5p was found to be rich in C26 cells and C26 exosomes, and miR-183-5p mimic could directly induce atrophy of C2C12 myotubes. Carnosol at 5 to 20 μM could dose-dependently ameliorate the myotube atrophy induced by miR-183-5p. Four and a half LIM domain protein 1 (FHL1) was shown to be the direct target of miR-183-5p. Increase in myostatin, p-Smad3, MuRF-1, Atrogin-1, HIF-1α and p-STAT3 and decrease in mitochondrial respiration were also induced by miR-183-5p mimic in C2C12 myotubes. Carnosol could not affect the decrease in FHL-1 and the activation of STAT3 pathway but could significantly alleviate the increase in myostatin, p-Smad3, MuRF-1, Atrogin-1 and the decrease in mitochondrial respiration induced by miR-183-5p. The protective effects of carnosol on myotubes against atrophy of C2C12 myotubes induced by miR-183-5p, based on both its inhibiting effects on MuRF-1 and Atrogin-1-mediated protein degradation and its ability of keeping the mitochondrial respiration, might contribute to its ameliorating effects on cancer cachexia.
摘要：
癌症来源的外泌体参与癌症恶病质的发展。鼠尾草,在我们之前的研究中，它对C26荷瘤小鼠的癌症恶病质表现出改善作用，本研究减轻了C26肿瘤细胞外泌体诱导的C2C12肌管萎缩。发现MiR-183-5p富含C26细胞和C26外泌体，miR-183-5p模拟物可以直接诱导C2C12肌管萎缩。5至20μM的鼠尾草酚可以剂量依赖性地改善miR-183-5p诱导的肌管萎缩。四个半LIM结构域蛋白1(FHL1)显示为miR-183-5p的直接靶标。肌肉生长抑制素增加，在C2C12肌管中，miR-183-5p模拟物也诱导了p-Smad3，MuRF-1，Atrogin-1，HIF-1α和p-STAT3以及线粒体呼吸的减少。鼠尾草酚不影响FHL-1的降低和STAT3通路的激活，但可以明显减轻肌肉生长抑制素的增加，p-Smad3，MuRF-1，Atrogin-1和miR-183-5p诱导的线粒体呼吸减少。鼠尾草酚对miR-183-5p诱导的C2C12肌管萎缩的保护作用基于其对MuRF-1和Atrogin-1介导的蛋白质降解的抑制作用以及其保持线粒体呼吸的能力，可能有助于其对癌症恶病质的改善作用。
