Forkhead Box M1 Transcriptionally Regulates the Expression of Long Noncoding RNAs Snhg8 and Gm26917 to Promote Proliferation and Survival of Muscle Satellite Cells.

Abstract

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. Stem Cells 2018;36:1097-1108.