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FoxM1 Regulates Muscle Stem Cell Proliferation and Survival via long non-coding RNAs

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Review of “Forkhead Box M1 Transcriptionally Regulates the Expression of Long Noncoding RNAs Snhg8 and Gm26917 to Promote Proliferation and Survival of Muscle Satellite Cells” from STEM CELLS by Stuart P. Atkinson

Muscle stem cells, also known as satellite cells (SCs), aid in the homeostasis and regeneration of skeletal muscle thanks to their ability to undergo quiescence, self‐renewal, and differentiation in response to stimuli including damage or exercise-related contraction [1, 2]. To build a fuller picture of the mechanisms that control these interrelated processes in SCs, researchers led by Jieping Chen and Yu Hou (Third Military Medical University, Chongqing, PR China) investigated the involvement of forkhead box M1 (FoxM1) [3], a transcription factor with diverse functions in a range of stem cells. In a new STEM CELLS study, Chen et al. now report that FoxM1 controls the proliferation and survival of SCs, partly through the regulation of the Snhg8 and Gm26917 long non-coding RNAs (lncRNAs) [4].

Initial analyses by the authors uncovered evidence of ubiquitous expression of FoxM1 in both quiescent and activated SCs, with Fox1M loss in vitro and in vivo leading to reduced SC proliferation and increased apoptosis. Differential gene expression analysis then highlighted the altered expression of 49 lncRNAs following FoxM1 knockout in C2C12 cells, a murine myoblast cell line widely investigated as a model of myogenesis [5]. 

Interestingly, FoxM1 directly targeted and increased the expression of two lncRNAs, Snhg8 (small nucleolar RNA host gene 8) and Gm26917 (predicted gene, 26917), via binding to consensus sites present in their promoter sequences. Interestingly, Snhg8 expression promoted proliferation by enhancing ribosomal protein transcription, while Gm26917 expression promoted survival by acting as a competing endogenous RNA for the apoptosis-inducing microRNA‐29b (miRNA sponge) in both murine myoblasts and SCs.

Overall, this muscle-strengthening study suggests that the FoxM1‐Snhg8 and FoxM‐Gm26917 axes promote the maintenance of muscle stem cells in mice by regulating their proliferation and survival, respectively. Furthermore, the authors provide insight into the network or lncRNA genes regulated by FoxM1; what FoxM1-lncRNAs play crucial roles in other stem cell types?

For more on FoxM1, lncRNAs, and the mechanisms controlling muscle stem cells, stay tuned to the Stem Cells Portal!

References

  1. Rozo M, Li L, and Fan C-M, Targeting β1-integrin signaling enhances regeneration in aged and dystrophic muscle in mice. Nature Medicine 2016;22:889.
  2. Urciuolo A, Quarta M, Morbidoni V, et al., Collagen VI regulates satellite cell self-renewal and muscle regeneration. Nature Communications 2013;4:1964.
  3. Bella L, Zona S, Nestal de Moraes G, et al., FOXM1: A key oncofoetal transcription factor in health and disease. Seminars in Cancer Biology 2014;29:32-39.
  4. Chen Z, Bu N, Qiao X, et al., Forkhead Box M1 Transcriptionally Regulates the Expression of Long Noncoding RNAs Snhg8 and Gm26917 to Promote Proliferation and Survival of Muscle Satellite Cells. STEM CELLS 2018;36:1097-1108.
  5. Zhou L, Sun K, Zhao Y, et al., Linc-YY1 promotes myogenic differentiation and muscle regeneration through an interaction with the transcription factor YY1. Nature Communications 2015;6:10026.