In mammals, microRNAs can be actively secreted from cells to blood. miR‐29b‐3p has been shown to play a pivotal role in muscle atrophy, but its role in intercellular communication is largely unknown. Here, we showed that miR‐29b‐3p was upregulated in normal and premature aging mouse muscle and plasma. miR‐29b‐3p was also upregulated in the blood of aging individuals, and circulating levels of miR‐29b‐3p were negatively correlated with relative appendicular skeletal muscle. Consistently, miR‐29b‐3p was observed in exosomes isolated from long‐term differentiated atrophic C2C12 cells. When C2C12‐derived miR‐29b‐3p‐containing exosomes were uptaken by neuronal SH‐SY5Y cells, increased miR‐29b‐3p levels in recipient cells were observed. Moreover, miR‐29b‐3p overexpression led to downregulation of neuronal‐related genes and inhibition of neuronal differentiation. Interestingly, we identified HIF1α‐AS2 as a novel c‐FOS targeting lncRNA that is induced by miR‐29b‐3p through down‐modulation of c‐FOS and is required for miR‐29b‐3p‐mediated neuronal differentiation inhibition. Our results suggest that atrophy‐associated circulating miR‐29b‐3p may mediate distal communication between muscle cells and neurons.

中文翻译：

---

神经元功能障碍中与肌肉萎缩相关的肌管来源的外泌体microRNA：以编码RNA和长非编码RNA为靶标。

在哺乳动物中，microRNA可以从细胞主动分泌到血液中。已证明miR‐29b‐3p在肌肉萎缩中起关键作用，但在细胞间通讯中的作用尚不清楚。在这里，我们显示了正常和早衰小鼠肌肉和血浆中的miR‐29b‐3p上调。衰老个体的血液中miR‐29b‐3p也上调，而miR‐29b‐3p的循环水平与相对的阑尾骨骼肌呈负相关。一致地，从长期分化的萎缩性C2C12细胞中分离出的外泌体中观察到了miR-29b-3p。当神经元SH-SY5Y细胞摄取C2C12衍生的含miR-29b-3p的外泌体时，观察到受体细胞中miR-29b-3p的水平增加。此外，miR‐29b‐3p的过度表达导致神经元相关基因的下调和神经元分化的抑制。有趣的是，我们将HIF1α-AS2确定为靶向lncRNA的新型c-FOS，它是由miR-29b-3p通过下调c-FOS诱导的，并且是miR-29b-3p介导的神经元分化抑制所必需的。我们的研究结果表明，与萎缩相关的循环miR-​​29b-3p可能介导肌肉细胞与神经元之间的远端通讯。