Cited by 23Mesenchymal stem cell researchNeurogenesis and neuroplasticity mechanismsMicroRNA in disease regulation

MiR-124 Promote Neurogenic Transdifferentiation of Adipose Derived Mesenchymal Stromal Cells Partly through RhoA/ROCK1, but Not ROCK2 Signaling Pathway

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Wang, Ye, Wang, Desheng, Guo, Dawen·2016·PLOS ONE

Abstract

OBJECTIVE: Some recent studies suggest that multiple miRNAs might regulate neurogenic transdifferentiation of mesenchymal stromal cells (MSCs). In the present study, we hypothesized that the miR-124 can repress the expression of RhoA upon the neurogenesis of adipose derived MSCs (ADMSCs). METHODS: MiRNA expression dynamics during neurogenic transdifferentiation of ADMSCs were measured. The expression of neuron-specific enolase (NSE), Tuj-1 (Neuron-specific class III beta-tubulin) and glial fibrillary acidic protein (GFAP), as well as electrophysiological properties, were detected after neurogenic transdifferentiation. The targeting of miR-124 over RhoA was verified by dual luciferase assay, qRT-PCR and western blot. The functions of miR-124 and the RhoA/ROCK signaling pathway were studied using gain and loss of function experiments in vitro. RESULTS: MiR-124 is significantly upregulated during neurogenic transdifferentiation of ADMSCs. Knockdown of endogenous miR-124 hampered neurogenic transdifferentiation and the acquired electrophysiological properties. MiR-124 could directly target RHOA mRNA and repress its expression, through which it increased the proportion of transdifferentiated (transdiff.) cells with positive NSE, Tuj-1 and GFAP. RhoA/ROCK1, but not ROCK2 is a downstream signaling pathway of miR-124 in the process of transdifferentiation. CONCLUSION: MiR-124 is an important miRNA modulating neurogenic transdifferentiation of ADMSCs at least partly via the miR-124/RhoA/ROCK1 signaling pathway. These findings provided some fundamental information for future use of ADMSCs as an agent for regenerative medicine and cell therapy for neurological diseases.

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  • miR-142 promoted neurogenic differentiation of adipose-derived stem cells by targeting RhoA.

    “Furthermore, miR-142 promoted neurogenic differentiation of adipose-derived stem cells by targeting RhoA [114,115].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [115]

    The Results section identifies miR-124—not miR-142—as the microRNA that directly targets RhoA. The Abstract’s Results also attribute the increased neurogenic transdifferentiation of adipose-derived mesenchymal stromal cells to miR-124. (LLM, conf=0.90)

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  1. [2]de Girolamo L, Lucarelli E, Alessandri G, Avanzini MA, Bernardo ME, Biagi E, et al Mesenchymal stem/stromal cells: a new ''cells as drugs'' paradigm. Efficacy and critical aspects in cell therapy. Current pharmaceutical design. 2013; 19(13): 2459– 73. 23278600 PMC3788322
  2. [3]Cao W, Li P. Effectiveness and Safety of Autologous Bone Marrow Stromal Cells Transplantation After Ischemic Stroke: A Meta-Analysis. Medical science monitor: international medical journal of experimental and clinical research. 2015; 21: 2190– 5. 10.12659/MSM.895081 26215395 PMC4523068 · DOI
  3. [4]Secunda R, Vennila R, Mohanashankar AM, Rajasundari M, Jeswanth S, Surendran R. Isolation, expansion and characterisation of mesenchymal stem cells from human bone marrow, adipose tissue, umbilical cord blood and matrix: a comparative study. Cytotechnology. 2014 10.1007/s10616-014-9718-z PMC4545441 24798808 · DOI
  4. [5]Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2): 281– 97. 14744438
  5. [6]Duan P, Sun S, Li B, Huang C, Xu Y, Han X, et al miR-29a modulates neuronal differentiation through targeting REST in mesenchymal stem cells. PloS one. 2014; 9(5): e97684 10.1371/journal.pone.0097684 24841827 PMC4026383 · DOI
  6. [7]Mondanizadeh M, Arefian E, Mosayebi G, Saidijam M, Khansarinejad B, Hashemi SM. MicroRNA-124 regulates neuronal differentiation of mesenchymal stem cells by targeting Sp1 mRNA. Journal of cellular biochemistry. 2015; 116(6): 943– 53. 10.1002/jcb.25045 25559917 · DOI
  7. [8]Cao X, Pfaff SL, Gage FH. A functional study of miR-124 in the developing neural tube. Genes & development. 2007; 21(5): 531– 6. 10.1101/gad.1519207 17344415 PMC1820895 · DOI
  8. [9]Makeyev EV, Zhang J, Carrasco MA, Maniatis T. The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Molecular cell. 2007; 27(3): 435– 48. 10.1016/j.molcel.2007.07.015 17679093 PMC3139456 · DOI · Paper page
  9. [10]Cheng LC, Pastrana E, Tavazoie M, Doetsch F. miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nature neuroscience. 2009; 12(4): 399– 408. 10.1038/nn.2294 19287386 PMC2766245 · DOI · Paper page
  10. [11]Silber J, Lim DA, Petritsch C, Persson AI, Maunakea AK, Yu M, et al miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC medicine. 2008; 6: 14 10.1186/1741-7015-6-14 18577219 PMC2443372 · DOI · Paper page
  11. [12]Yu JY, Chung KH, Deo M, Thompson RC, Turner DL. MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation. Experimental cell research. 2008; 314(14): 2618– 33. 10.1016/j.yexcr.2008.06.002 18619591 PMC2702206 · DOI
  12. [13]Wheeler AP, Ridley AJ. Why three Rho proteins? RhoA, RhoB, RhoC, and cell motility. Experimental cell research. 2004; 301(1): 43– 9. 10.1016/j.yexcr.2004.08.012 15501444 · DOI
  13. [14]Pacary E, Tixier E, Coulet F, Roussel S, Petit E, Bernaudin M. Crosstalk between HIF-1 and ROCK pathways in neuronal differentiation of mesenchymal stem cells, neurospheres and in PC12 neurite outgrowth. Molecular and cellular neurosciences. 2007; 35(3): 409– 23. 10.1016/j.mcn.2007.04.002 17493827 · DOI
  14. [15]Liu X, Zhang Z, Yan X, Liu H, Zhang L, Yao A, et al The Rho kinase inhibitor Y-27632 facilitates the differentiation of bone marrow mesenchymal stem cells. Journal of molecular histology. 2014; 45(6): 707– 14. 10.1007/s10735-014-9594-z 25178638 · DOI
  15. [16]Leong WS, Wu SC, Pal M, Tay CY, Yu H, Li H, et al Cyclic tensile loading regulates human mesenchymal stem cell differentiation into neuron-like phenotype. Journal of tissue engineering and regenerative medicine. 2012; 6 Suppl 3: s68– 79. 10.1002/term.1548 22777815 · DOI
  16. [17]Salehi H, Amirpour N, Niapour A, Razavi S. An Overview of Neural Differentiation Potential of Human Adipose Derived Stem Cells. Stem cell reviews. 2015 10.1007/s12015-015-9631-7 26490462 · DOI
  17. [18]Bacci A, Verderio C, Pravettoni E, Matteoli M. Synaptic and intrinsic mechanisms shape synchronous oscillations in hippocampal neurons in culture. The European journal of neuroscience. 1999; 11(2): 389– 97. 10051739
  18. [19]Neo WH, Yap K, Lee SH, Looi LS, Khandelia P, Neo SX, et al MicroRNA miR-124 controls the choice between neuronal and astrocyte differentiation by fine-tuning Ezh2 expression. The Journal of biological chemistry. 2014; 289(30): 20788– 801. 10.1074/jbc.M113.525493 24878960 PMC4110287 · DOI
  19. [20]Santos MC, Tegge AN, Correa BR, Mahesula S, Kohnke LQ, Qiao M, et al miR-124, -128, and -137 Orchestrate Neural Differentiation by Acting on Overlapping Gene Sets Containing a Highly Connected Transcription Factor Network. Stem cells. 2015 10.1002/stem.2204 26369286 · DOI
  20. [21]Zou D, Chen Y, Han Y, Lv C, Tu G. Overexpression of microRNA-124 promotes the neuronal differentiation of bone marrow-derived mesenchymal stem cells. Neural regeneration research. 2014; 9(12): 1241– 8. 10.4103/1673-5374.135333 25206789 PMC4146284 · DOI
  21. [22]Mareschi K, Rustichelli D, Comunanza V, De Fazio R, Cravero C, Morterra G, et al Multipotent mesenchymal stem cells from amniotic fluid originate neural precursors with functional voltage-gated sodium channels. Cytotherapy. 2009; 11(5): 534– 47. 10.1080/14653240902974024 19548144 · DOI
  22. [23]Subbarao RB, Ullah I, Kim EJ, Jang SJ, Lee WJ, Jeon RH, et al Characterization and evaluation of neuronal trans-differentiation with electrophysiological properties of mesenchymal stem cells isolated from porcine endometrium. International journal of molecular sciences. 2015; 16(5): 10934– 51. 10.3390/ijms160510934 26006231 PMC4463684 · DOI
  23. [24]Bossio C, Mastrangelo R, Morini R, Tonna N, Coco S, Verderio C, et al A simple method to generate adipose stem cell-derived neurons for screening purposes. Journal of molecular neuroscience: MN. 2013; 51(2): 274– 81. 10.1007/s12031-013-9985-8 23468184 · DOI
  24. [25]Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S, Lipton SA, et al Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell stem cell. 2011; 9(2): 113– 8. 10.1016/j.stem.2011.07.002 21802386 PMC4567246 · DOI
  25. [26]Yoo AS, Sun AX, Li L, Shcheglovitov A, Portmann T, Li Y, et al MicroRNA-mediated conversion of human fibroblasts to neurons. Nature. 2011; 476(7359): 228– 31. 10.1038/nature10323 21753754 PMC3348862 · DOI · Paper page
  26. [27]Gu X, Meng S, Liu S, Jia C, Fang Y, Li S, et al miR-124 represses ROCK1 expression to promote neurite elongation through activation of the PI3K/Akt signal pathway. Journal of molecular neuroscience: MN. 2014; 52(1): 156– 65. 10.1007/s12031-013-0190-6 24338057 · DOI
  27. [28]Zhao CF, Liu Y, Ni YL, Yang JW, Hui HD, Sun ZB, et al SCIRR39 promotes neurite extension via RhoA in NGF-induced PC12 cells. Developmental neuroscience. 2013; 35(5): 373– 83. 10.1159/000350715 24021527 · DOI
  28. [29]Chen K, He H, Xie Y, Zhao L, Zhao S, Wan X, et al miR-125a-3p and miR-483-5p promote adipogenesis via suppressing the RhoA/ROCK1/ERK1/2 pathway in multiple symmetric lipomatosis. Scientific reports. 2015; 5: 11909 10.1038/srep11909 26148871 PMC4493643 · DOI
  29. [30]Lin X, Wu L, Zhang Z, Yang R, Guan Q, Hou X, et al MiR-335-5p promotes chondrogenesis in mouse mesenchymal stem cells and is regulated through two positive feedback loops. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research. 2014; 29(7): 1575– 85. 10.1002/jbmr.2163 24347469 · DOI

Cited by

Sorted by citations

Authors
Wang, Y., Wang, D., & Guo, D.
Affiliations
Harbin Medical University (CN)
Corresponding author
Guo, Dawen
Venue
PLOS ONE
Published
2016-01-08
Volume
11
Issue
1
Pages
e0146646
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2231448704
Cited by
23
References
1
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 3
FWCI
1.63
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
miR-124, adipose-derived mesenchymal stromal cells, RhoA/ROCK1 signaling, ROCK2, microRNA regulation, neuron-specific enolase, Tuj1, glial fibrillary acidic protein, electrophysiological properties
MeSH terms
Adipose Tissue, Animals, Cells, Cultured, Humans, Neurons, RNA, Messenger, Signal Transduction, Up-Regulation, Rats, Sprague-Dawley, Patch-Clamp Techniques, rhoA GTP-Binding Protein, RNA Interference, RNA, Small Interfering, MicroRNAs, Rats, Cell Transdifferentiation, rho-Associated Kinases, Neurogenesis, HEK293 Cells, Mesenchymal Stem Cells, Real-Time Polymerase Chain Reaction

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