Abstract
MiR-205 plays an important role during adipogenesis by modulating the Wnt signaling pathway. Here, we report that miR-205 can regulate the differentiation of 3T3-L1 preadipocyte cells by targeting glycogen synthase kinase 3 beta (GSK-3β), which is a negative regulatory factor of Wnt signaling. When transiently overexpressed in 3T3-L1 cells, miR-205 suppressed the translation of GSK-3β, resulting in increased expression of β-catenin, which can promote cell proliferation by facilitating the transcription of the Wnt target genes cyclin D1 and c-Myc. However, stable overexpression of miR-205 in 3T3-L1 cells did not show any apparent inhibitory effect on adipogenic differentiation. While endogenous miR-205 was inhibited in 3T3-L1 cells, the adipogenesis marker gene, C/EBPα, was significantly activated and more lipid droplets appeared in differentiated adipocytes. However, systemic silencing of miR-205 in mice by using a locked-nucleic-acid-modified oligonucleotide (LNA-antimiR) did not lead to any observable increase in adipose tissue differentiation, implying that, as opposed to the findings from 3T3-L1 cells, miR-205 is dispensable for adipose tissue development in mice.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Bennett CN, Ross SE, Longo KA, Bajnok L, Hemati N, Johnson KW, Harrison SD, MacDougald OA (2002) Regulation of Wnt signaling during adipogenesis. J Biol Chem 277:30998–31004
Christodoulides C, Lagathu C, Sethi JK, Vidal-Puig A (2009) Adipogenesis and WNT signaling. Trends Endocrinol Metab 20:16–24
Dar AA, Majid S, de Semir D, Nosrati M, Bezrookove V, Kashani-Sabet M (2011) miRNA-205 suppresses melanoma cell proliferation and induces senescence via regulation of E2F1 protein. J Biol Chem 286:16606–16614
Elia L, Quintavalle M, Zhang J, Contu R, Cossu L, Latronico MV, Peterson KL, Indolfi C, Catalucci D, Chen J, Courtneidge SA, Condorelli G (2009) The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease. Cell Death Differ 16:1590–1598
Guo Y, Mo D, Zhang Y, Zhang Y, Cong P, Xiao S, He Z, Liu X, Chen Y (2012) MicroRNAome comparison between intramuscular and subcutaneous vascular stem cell adipogenesis. PLoS ONE 7:e45410
Hagman Z, Haflidadottir BS, Ceder JA, Larne O, Bjartell A, Lilja H, Edsjo A, Ceder Y (2013) miR-205 negatively regulates the androgen receptor and is associated with adverse outcome of prostate cancer patients. Br J Cancer 108:1668–1676
Hornstein E, Shomron N (2006) Canalization of development by microRNAs. Nat Genet 38:S20–S24
John E, Wienecke-Baldacchino A, Liivrand M, Heinäniemi M, Carlberg C, Sinkkonen L (2012) Dataset integration identifies transcriptional regulation of microRNA genes by PPARγ in differentiating mouse 3T3-L1 adipocytes. Nucleic Acids Res 40:4446–4460
Kim SY, Kim AY, Lee HW, Son YH, Lee GY, Lee JW, Lee YS, Kim JB (2010) miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression. Biochem Biophys Res Commun 392:323–328
Li Y-J, Wei Z-M, Meng Y-X, Ji X-R (2005) b-Catenin up-regulates the expression of cyclinD1, c-myc and MMP-7 in human pancreatic cancer: relationships with carcinogenesis and metastasis. World J Gastroenterol 11:2117–2123
Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810
Majid S, Saini S, Dar AA, Hirata H, Shahryari V, Tanaka Y, Yamamura S, Ueno K, Zaman MS, Singh K, Chang I, Deng G, Dahiya R (2011) MicroRNA-205 inhibits Src-mediated oncogenic pathways in renal cancer. Cancer Res 71:2611–2621
Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS (2003) Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. J Am Med Assn 289:76–79
Moldes M, Zuo Y, Morrison R, Silva D, Park B, Liu J, Farmer S (2003) Peroxisome-proliferator-activated receptor γ suppresses Wnt/β-catenin signaling during adipogenesis. Biochem J 376:607–613
Muratsu-Ikeda S, Nangaku M, Ikeda Y, Tanaka T, Wada T, Inagi R (2012) Downregulation of miR-205 modulates cell susceptibility to oxidative and endoplasmic reticulum stresses in renal tubular cells. PLoS ONE 7:e41462
Park CY, Choi YS, McManus MT (2010) Analysis of microRNA knockouts in mice. Hum Mol Genet 19:R169–R175
Qin L, Chen Y, Niu Y, Chen W, Wang Q, Xiao S, Li A, Xie Y, Li J, Zhao X, He Z, Mo D (2010) A deep investigation into the adipogenesis mechanism: profile of microRNAs regulating adipogenesis by modulating the canonical Wnt/beta-catenin signaling pathway. BMC Genom 11:320
Ross SE, Hemati N, Longo KA, Bennett CN, Lucas PC, Erickson RL, MacDougald OA (2000) Inhibition of adipogenesis by Wnt signaling. Science 289:950–953
Takahashi-Yanaga F, Sasaguri T (2008) GSK-3β regulates cyclin D1 expression: a new target for chemotherapy. Cell Signal 20:581–589
Wang H, Garzon R, Sun H, Ladner KJ, Singh R, Dahlman J, Cheng A, Hall BM, Qualman SJ, Chandler DS, Croce CM, Guttridge DC (2008a) NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell 14:369–381
Wang Q, Li YC, Wang J, Kong J, Qi Y, Quigg RJ, Li X (2008b) miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130. Proc Natl Acad Sci USA 105:2889–2894
Xin M, Small EM, Sutherland LB, Qi XX, McAnally J, Plato CF, Richardson JA, Bassel-Duby R, Olson EN (2009) MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. Gene Dev 23:2166–2178
Yi C, Xie WD, Li F, Lv Q, He J, Wu J, Gu D, Xu N, Zhang Y (2011) MiR-143 enhances adipogenic differentiation of 3T3-L1 cells through targeting the coding region of mouse pleiotrophin. FEBS Lett 585:3303–3309
Zeng C, Wang R, Li D, Lin XJ, Wei QK, Yuan Y, Wang Q, Chen W, Zhuang SM (2010) A novel GSK-3 beta-C/EBP alpha-miR-122-insulin-like growth factor 1 receptor regulatory circuitry in human hepatocellular carcinoma. Hepatology 52:1702–1712
Acknowledgments
This work was supported by the National S&T Major Project of China (Grant no. 2009ZX08010-017B), the National S&T Major Project of China (Grant no. 2011ZX08006-005), the National Science Foundation of China (Grant no. 30901018) and the China Agriculture Research System (CASR-36).
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Yu, J., Chen, Y., Qin, L. et al. Effect of miR-205 on 3T3-L1 preadipocyte differentiation through targeting to glycogen synthase kinase 3 beta. Biotechnol Lett 36, 1233–1243 (2014). https://doi.org/10.1007/s10529-014-1491-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-014-1491-8