Forkhead Box M1 Transcriptionally Regulates the Expression of Long Noncoding RNAs Snhg8 and Gm26917 to Promote Proliferation and Survival of Muscle Satellite Cells
Forkhead Box M1 Transcriptionally Regulates the Expression of Long Noncoding RNAs Snhg8 and Gm26917 to Promote Proliferation and Survival of Muscle Satellite Cells
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Forkhead Box M1 转录调节长非编码 RNA Snhg8 和 Gm26917 的表达，以促进肌肉卫星细胞的增殖和存活。
DOI：
10.1002/stem.2824
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发表时间：
2018-07-01
期刊：
影响因子：
5.2
通讯作者：
Hou, Yu
中科院分区：
文献类型：
--
作者：
Chen, Zhe;Bu, Nuping;Hou, Yu
转录因子 FoxM1 具有多种功能，包括调节细胞增殖、分化、衰老、凋亡和组织稳态。然而，FoxM1在肌肉卫星细胞（SCs）中的作用仍不清楚。在本研究中，我们证明了 FoxM1 对卫星细胞的增殖和存活至关重要。重要的是，我们发现长非编码 RNA（lncRNA）Snhg8 和 Gm26917 分别显著调控 SCs 的增殖和凋亡，而这些 lncRNA 在 SCs 中直接受 FoxM1 的调控。从机制上看，Snhg8通过促进核糖体蛋白的转录来维持SCs的增殖，而Gm26917则作为microRNA-29b的竞争内源RNA，加速了SCs的凋亡。在小鼠骨骼肌中，条件性敲除 FoxM1 会导致 SCs 增殖减少和凋亡增加。因此，我们的研究揭示了FoxM1在SCs中以前未被发现的作用，并发现了两个lncRNA，即Snhg8和Gm26917，它们是FoxM1在调节SCs增殖和存活中的新靶点。
Multiple functions have been proposed for transcription factor FoxM1, including the regulation of cell proliferation, differentiation, senescence, apoptosis, and tissue homeostasis. However, the role of FoxM1 in muscle satellite cells (SCs) remains unclear. In the present study, we demonstrated that FoxM1 was essential for the proliferation and survival of SCs. Crucially, we found that long noncoding RNAs (lncRNAs) Snhg8 and Gm26917 significantly regulated the proliferation and apoptosis of SCs, respectively, and these lncRNAs were directly regulated by FoxM1 in SCs. Mechanistically, Snhg8 sustained SCs proliferation by promoting the transcription of ribosomal proteins, while Gm26917 acted as a competing endogenous RNA for microRNA-29b, which accelerated apoptosis of SCs. In mice, conditional knockout of FoxM1 in skeletal muscle resulted in decreased proliferation and increased apoptosis of SCs. Thus, our studies revealed a previously unrecognized role of FoxM1 in SCs and uncovered two lncRNAs, Snhg8 and Gm26917, which function as novel targets of FoxM1 in the regulation of SCs proliferation and survival.