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miR-377-3p regulates adipogenic differentiation of human bone marrow mesenchymal stem cells by regulating LIFR

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Abstract

MicroRNAs are members of the family of non-coding small RNAs that regulate gene expression either by inhibiting mRNA translation or by promoting mRNA degradation at the post-transcriptional level. They play an important role in the differentiation of human bone marrow mesenchymal stem cells (hMSCs) into adipocytes. However, the role of microRNAs in this process remains to be poorly understood. Here, we observed that miR-377-3p expression was markedly decreased during adipogenic differentiation of hMSCs. Overexpression of miR-377-3p decreased adipocyte differentiation and downregulated the expression of adipogenic markers. Meanwhile, bioinformatics-based studies suggested that LIFR is a target of miR-377-3p. Further analysis confirmed that expression of LIFR present markedly increased during adipogenic differentiation of hMSCs. In addition, downregulation expression of LIFR significantly inhibited the process of adipocyte differentiation. To confirm the relation between miR-377-3p and LIFR, luciferase reporter assays were carried out. The results indicated that miR-377-3p bound directly to the 3′-untranslated region of LIFR. These data indicate that miR-377-3p suppressed adipogenesis of hMSCs by targeting LIFR, which provides novel insights into the molecular mechanism of miRNA-mediated cellular differentiation.

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References

  1. Li H, Chen X, Guan L, Qi Q, Shu G, Jiang Q, Yuan L, Xi Q, Zhang Y (2013) MiRNA-181a regulates adipogenesis by targeting tumor necrosis factor-alpha (TNF-alpha) in the porcine model. PLoS ONE 8:e71568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kopelman PG (2000) Obesity as a medical problem. Nature 404:635–643

    Article  CAS  PubMed  Google Scholar 

  3. Qiu J, Zhou XG, Zhou XY, Zhu C, Shi CM, Ji CB, Cheng R, Li Y, Guo XR (2013) Characterization of microRNA expression profiles in 3T3-L1 adipocytes overexpressing C10orf116. Mol Biol Rep 40:6469–6476

    Article  CAS  PubMed  Google Scholar 

  4. Otto TC, Lane MD (2005) Adipose development: from stem cell to adipocyte. Crit Rev Biochem Mol Biol 40:229–242

    Article  CAS  PubMed  Google Scholar 

  5. Pittenger MF, Mackay AM, Beck SC, Jaiswal PK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  CAS  PubMed  Google Scholar 

  6. Helder MN, Knippenberg M, Klein-Nulend J, Wuisman PI (2007) Stem cells from adipose tissue allow challenging new concepts for regenerative medicine. Tissue Eng 13:1799–1808

    Article  CAS  PubMed  Google Scholar 

  7. Barry F, Boynton RE, Liu B, Murphy JM (2001) Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components. Exp Cell Res 268:189–200

    Article  CAS  PubMed  Google Scholar 

  8. Arinzeh TL (2005) Mesenchymal stem cells for bone repair: preclinical studies and potential orthopedic applications. Foot Ankle Clin 10:651–665

    Article  PubMed  Google Scholar 

  9. Subash-Babu P, Alshatwi AA (2012) Aloe-emodin inhibits adipocyte differentiation and maturation during in vitro human mesenchymal stem cell adipogenesis. J Biochem Mol Toxicol 26:291–300

    Article  CAS  PubMed  Google Scholar 

  10. Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355

    Article  CAS  PubMed  Google Scholar 

  11. Xie H, Lim B, Lodish HF (2009) MicroRNAs induced during adipogenesis that accelerate fat cell development are downregulated in obesity. Diabetes 58:1050–1057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Karbiener M, Neuhold C, Opriessnig P, Prokesch A, Bogner-Strauss JG, Scheideler M (2011) MicroRNA-30c promotes human adipocyte differentiation and co-represses PAI-1 and ALK2. RNA Biol 8:850–860

    Article  CAS  PubMed  Google Scholar 

  13. Ling HY, Wen GB, Feng SD, Tuo QH, Ou HS, Yao CH, Zhu BY, Gao ZP, Zhang L, Liao DF (2011) MicroRNA-375 promotes 3T3-L1 adipocyte differentiation through modulation of extracellular signal-regulated kinase signaling. Clin Exp Pharmacol Physiol 38:239–246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu S, Yang Y, Wu J (2011) TNF alpha-induced up-regulation of miR-155 inhibits adipogenesis by down-regulating early adipogenic transcription factors. Biochem Biophys Res Commun 414:618–624

    Article  CAS  PubMed  Google Scholar 

  15. Peng Y, Xiang H, Chen C, Zheng R, Chai J, Peng J, Jiang S (2013) MiR-224 impairs adipocyte early differentiation and regulates fatty acid metabolism. Int J Biochem Cell Biol 45:1585–1593

    Article  CAS  PubMed  Google Scholar 

  16. del Valle I, Rudloff S, Carles A, Li Y, Liszewska E, Vogt R, Kemler R (2013) E-cadherin is required for the proper activation of the Lifr/Gp130 signaling pathway in mouse embryonic stem cells. Development 140:1684–1692

    Article  PubMed  Google Scholar 

  17. Pan W, Cain C, Yu Y, Kastin AJ (2006) Receptor-mediated transport of LIF across blood-spinal cord barrier is upregulated after spinal cord injury. J Neuroimmunol 174:119–125

    Article  CAS  PubMed  Google Scholar 

  18. Plun-Favreau H, Perret D, Diveu C, Froger J, Chevalier S, Lelièvre E, Gascan H, Chabbert M (2003) Leukemia inhibitory factor (LIF), cardiotrophin-1, and oncostatin M share structural binding determinants in the immunoglobulin-like domain of LIF receptor. J Biol Chem 278:27169–27179

    Article  CAS  PubMed  Google Scholar 

  19. Hwang JH, Byun MR, Kim AR, Kim KM, Cho HJ, Lee YH, Kim J, Jeong MG, Hwang ES, Hong JH (2015) Extracellular matrix stiffness regulates osteogenic differentiation through MAPK activation. PLoS ONE 10:e0135519

    Article  PubMed  PubMed Central  Google Scholar 

  20. Huang E, Zhu G, Jiang W, Yang K, Gao Y, Luo Q, Gao JL, Kim SH, Liu X, Li M, Shi Q, Hu N, Wang L, Liu H (2012) Growth hormone synergizes with BMP9 in osteogenic differentiation by activating the JAK/STAT/IGF1 pathway in murine multilineage cells. J Bone Miner Res 27:1566–1575

    Article  CAS  PubMed  Google Scholar 

  21. Piekorz RP, Rinke R, Gouilleux F, Neumann B, Groner B, Hocke GM (1998) Modulation of the activation status of Stat5a during LIF-induced differentiation of M1 myeloid leukemia cells. Biochim Biophys Acta 1402:313–323

    Article  CAS  PubMed  Google Scholar 

  22. Sims NA, Johnson RW (2012) Leukemia inhibitory factor: a paracrine mediator of bone metabolism. Growth Factors 30:76–87

    Article  CAS  PubMed  Google Scholar 

  23. Malaval L, Gupta AK, Aubin JE (1995) Leukemia inhibitory factor inhibits osteogenic differentiation in rat calvaria cell cultures. Endocrinology 136:1411–1418

    Article  CAS  PubMed  Google Scholar 

  24. Gangaraju VK, Lin H (2009) MicroRNAs: key regulators of stem cells. Nat Rev Mol Cell Biol 10:116–125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lakshmipathy U, Hart RP (2008) Concise review: MicroRNA expression in multipotent mesenchymal stromal cells. Stem Cells 26:356–363

    Article  CAS  PubMed  Google Scholar 

  26. Farmer SR (2006) Transcriptional control of adipocyte formation. Cell Metab 4:263–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kudo M, Sugawara A, Uruno A, Takeuchi K, Ito S (2004) Transcription suppression of peroxisome proliferator-activated receptor gamma2 gene expression by tumor necrosis factor alpha via an inhibition of CCAAT/enhancer-binding protein delta during the early stage of adipocyte differentiation. Endocrinology 145:4948–4956

    Article  CAS  PubMed  Google Scholar 

  28. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM (2000) Transcriptional regulation of adipogenesis. Genes Dev 14:1293–1307

    CAS  PubMed  Google Scholar 

  29. Zhang J, Huang Y, Shao H, Bi Q, Chen J, Ye Z (2017) Grape seed procyanidin B2 inhibits adipogenesis of 3T3-L1 cells by targeting peroxisome proliferator-activated receptor γ with miR-483-5p involved mechanism. Biomed Pharmacother 86:292–296

    Article  CAS  PubMed  Google Scholar 

  30. Zehavi L, Schayek H, Jacob-Hirsch J, Sidi Y, Leibowitz-Amit R, Avni D (2015) MiR-377 targets E2F3 and alters the NF-kB signaling pathway through MAP3K7 in malignant melanoma. Mol Cancer 14:68

    Article  PubMed  PubMed Central  Google Scholar 

  31. Wang R, Ma Y, Yu D, Zhao J, Ma P (2015) miR-377 functions as a tumor suppressor in human clear cell renal cell carcinoma by targeting ETS1. Biomed Pharmacother 70:64–71

    Article  CAS  PubMed  Google Scholar 

  32. Meng F, Zhang L, Shao Y, Ma Q, Lv H (2015) MicroRNA-377 inhibits non-small-cell lung cancer through targeting AEG-1. Int J Clin Exp Pathol 8:13853–13863

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang Q, Wang Y, Minto AW, Wang J, Shi Q, Li X, Quigg RJ (2008) MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy. FASEB J 22:4126–4135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Peng J, Wu Y, Deng Z, Zhou Y, Song T, Yang Y, Zhang X, Xu T, Xia M, Cai A, Liu Z, Peng J (2017) MiR-377 promotes white adipose tissue inflammation and decreases insulin sensitivity in obesity via suppression of sirtuin-1 (SIRT1). Oncotarget 8:70550–70563

    PubMed  PubMed Central  Google Scholar 

  35. Aubert J, Dessolin S, Belmonte N, Li M, McKenzie FR, Staccini L, Villageois P, Barhanin B, Vernallis A, Smith AG, Ailhaud G, Dani C (1999) Leukemia inhibitory factor and its receptor promote adipocyte differentiation via the mitogen-activated protein kinase cascade. J Biol Chem 274:24965–24972

    Article  CAS  PubMed  Google Scholar 

  36. Natesh K, Bhosale D, Desai A, Chandrika G, Pujari R, Jagtap J, Chugh A, Ranade D, Shastry P (2015) Oncostatin-M differentially regulates mesenchymal and proneural signature genes in gliomas via STAT3 signaling. Neoplasia 17:225–237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wagener EM, Aurich M, Aparicio-Siegmund S, Floss DM, Garbers C, Breusing K, Rabe B, Schwanbeck R, Grötzinger J, Rose-John S, Scheller J (2014) The amino acid exchange R28E in ciliary neurotrophic factor (CNTF) abrogates interleukin-6 receptor-dependent but retains CNTF receptor-dependent signaling via glycoprotein 130 (gp130)/leukemia inhibitory factor receptor (LIFR). J Biol Chem 289:18442–184450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Liu GX, Zhu JC, Chen XY, Zhu AZ, Liu CC, Lai Q, Chen ST (2015) Inhibition of adipogenic differentiation of bone marrow mesenchymal stem cells by erythropoietin via activating ERK and P38 MAPK. Genet Mol Res 14:6968–6977

    Article  CAS  PubMed  Google Scholar 

  39. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Floyd ZE, Stephens JM (2012) Controlling a master switch of adipocyte development and insulin sensitivity: covalent modifications of PPARγ. Biochim Biophys Acta 1822:1090–1095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Furuhashi M, Tuncman G, Gorgun CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF, Sulsky R, Robl JA, Parker RA, Hotamisligil GS (2007) Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature 447:959–965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hwang CS, Mandrup S, MacDougald OS, Geiman DE, Lane MD (1996) Transcriptional activation of the mouse obese (ob) gene by CCAAT/enhancer binding protein alpha. Proc Natl Acad Sci USA 93:873–877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grants No. 81460221) and Jiangxi Province Natural Science Foundation of China (No. 20161BAB205197).

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Correspondence to Jianjun Xiong or Tao Wang.

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Li, X., Yang, Y., Yan, R. et al. miR-377-3p regulates adipogenic differentiation of human bone marrow mesenchymal stem cells by regulating LIFR. Mol Cell Biochem 449, 295–303 (2018). https://doi.org/10.1007/s11010-018-3366-0

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  • DOI: https://doi.org/10.1007/s11010-018-3366-0

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