Browse > Article
http://dx.doi.org/10.5352/JLS.2017.27.7.767

MicroRNA-200a/210 Controls Proliferation and Osteogenic Differentiation of Human Adipose Tissue Stromal Cells  

Kim, Young Suk (Department of Physiology, School of Medicine, Pusan National University)
Park, Hee Jeong (Department of Physiology, School of Medicine, Pusan National University)
Shin, Keun Koo (Department of Physiology, School of Medicine, Pusan National University)
Lee, Sun Young (Department of Physiology, School of Medicine, Pusan National University)
Bae, Yong Chan (Department of Plastic Surgery, School of Medicine, Pusan National University)
Jung, Jin Sup (Department of Physiology, School of Medicine, Pusan National University)
Publication Information
Journal of Life Science / v.27, no.7, 2017 , pp. 767-782 More about this Journal
Abstract
MicroRNAs control the differentiation and proliferation of human adipose tissue-derived stromal cells (hADSCs). However, the role of miR-200a and miR210 on the osteogenic differentiaton of hADSCs has not been determined. hADSCs were isolated from human adipose tissues. Direct binding of mircoRNA to target mRNAs was determined by luciferase assay of the constructs containing putative microRNA binding sites within 3' untranslated region of target mRNAs. Overexpression of miR-200a increased the proliferation and osteogenic differentiation of hADSCs, while causing downregulation of the levels of ZEB2. Inhibition of miR-200a with antisense RNAs inhibited the proliferation and osteogenic differentiation of hADSCs. Overexpression of miR-210 was found to inhibit the proliferation of hADSCs but increase the osteogenic differentiation, while causing downregulation of the levels of IGFBP3. Inhibition of miR-210 with antisense RNAs increased the proliferation but inhibited the osteogenic differentiation of hADSCs. Analysis of the luciferase activity of the constructs containing the miR-200a target site within the ZEB2 3' region and the miR-210 target site within the IGFBP3 3' region revealed lower activity in the miR-200a- or miR-210-transfected hADSCs than in control miRNA-transfected hADSCs. Downregulation of ZEB2 or IGFBP3 in the hADSCs showed similar effects on both their proliferation and osteogenic differentiation with that of miR-200a and miR-210 overexpression, respectively. The results of the current study indicate that miR-200a and miR-210 regulate the osteogenic differentiation and proliferation of hADSCs through the direct targeting of IGFBP3 and ZEB2, respectively.
Keywords
hADSC; miR-200a; miR-210; osteogenic differentiation; proliferation;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Ahmad, A., Aboukameel, A., Kong, D., Wang, Z., Sethi, S., Chen, W., Sarkar, F. H. and Raz, A. 2011. Phosphoglucose isomerase/autocrine motility factor mediates epithelial-mesenchymal transition regulated by miR-200 in breast cancer cells. Cancer Res. 71, 3400-3409.   DOI
2 Bodempudi, V., Hergert, P., Smith, K., Xia, H., Herrera, J., Peterson, M., Khalil, W., Kahm, J., Bitterman, P. B. and Henke, C. A. 2014. miR-210 promotes IPF fibroblast proliferation in response to hypoxia. Am. J. Physiol. Lung Cell. Mol. Physiol. 307, L283-294.   DOI
3 Brennecke, J., Hipfner, D. R., Stark, A., Russell, R. B. and Cohen, S. M. 2003. bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113, 25-36.   DOI
4 Chan, S. Y., Zhang, Y. Y., Hemann, C., Mahoney, C. E., Zweier, J. L. and Loscalzo, J. 2009. MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell. Metab. 10, 273-284.   DOI
5 Pampusch, M. S., Kamanga-Sollo, E., Hathaway, M. R., White, M. E. and Dayton, W. R. 2011. Low-density lipoprotein- related receptor protein 1 (LRP-1) is not required for insulin-like growth factor binding protein 3 (IGFBP-3) to suppress L6 myogenic cell proliferation. Domest. Anim. Endocrinol. 40, 197-204.   DOI
6 Puisségur, M. P., Mazure, N. M., Bertero, T., Pradelli, L., Grosso, S., Robbe-Sermesant, K., Maurin, T., Lebrigand, K., Cardinaud, B., Hofman, V., Fourre, S., Magnone, V., Ricci, J. E., Pouysségur, J., Gounon, P., Hofman, P., Barbry, P. and Mari, B. 2011. miR-210 is overexpressed in late stages of lung cancerand mediates mitochondrial alterations associated with modulation of HIF-1 activity. Cell Death Differ. 18, 465-478.   DOI
7 Cong, N., Du, P., Zhang, A., Shen, F., Su, J., Pu, P., Wang, T., Zjang, J., Kang, C. and Zhang, Q. 2013. Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/beta-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma. Oncol. Rep. 29, 1579-1587.   DOI
8 Fasanaro, P., D'Alessandra, Y., Di Stefano, V., Melchionna, R., Romani, S., Pompilio, G., Capogrossi, M. C. and Martelli, F. 2008. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J. Biol. Chem. 283, 15878-15883.   DOI
9 Park, S. M., Gaur, A. B., Lengyel, E. and Peter, M. E. 2008. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes. Dev. 22, 894-907.   DOI
10 Peng, C., Li, N., Ng, Y. K., Zhang, J., Meier, F., Theis, F. J., Merkenschlager, M., Chen, W., Wurst, W. and Prakash, N. 2012. A unilateral negative feedback loop between miR- 200 microRNAs and Sox2/E2F3 controls neural progenitor cell-cycle exit and differentiation. J. Neurosci. 32, 13292-13308.   DOI
11 Pulkkinen, K., Malm, T., Turunen, M., Koistinaho, J. and Ylä-Herttuala, S. 2008. Hypoxia induces microRNA miR-210 in vitro and in vivo ephrin-A3 and neuronal pentraxin 1 are potentially regulated by miR-210. FEBS. Lett. 582, 2397-2401.   DOI
12 Raucci, A., Bellosta, P., Grassi, R., Basilico, C. and Mansukhani, A. 2008. Osteoblast proliferation or differentiation is regulated by relative strengths of opposing signaling pathways. J. Cell. Physiol. 215, 442-451.   DOI
13 Gregory, P. A., Bracken, C. P., Smith, E., Bert, A. G., Wright, J. A., Roslan, S., Morris, M., Wyatt, L., Farshid, G., Lim, Y. Y., Lindeman, G. J., Shannon, M. F., Drew, P. A., Khew-Goodall, Y. and Goodall, G. J. 2011. An autocrine TGF-beta/ ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Mol. Biol. Cell 22, 1686-1698.   DOI
14 Firth, S. M and Baxter, R. C. 2002. Cellular actions of the insulin-like growth factor binding proteins. Endocr. Rev. 23, 824-854.   DOI
15 Gao, S. L., Wang, L. Z., Liu, H. Y., Liu, D. L., Xie, L. M. and Zhang, Z. W. 2014. miR-200a inhibits tumor proliferation by targeting AP-2gamma in neuroblastoma cells. Asian. Pac. J. Cancer Prev. 15, 4671-4676.   DOI
16 Giannakakis, A., Sandaltzopoulos, R., Greshock, J., Liang, S., Huang, J., Hasegawa, K, Li, C., O'Brien-Jenkins, A., Katsaros, D., Weber, B. L., Simon, C., Coukos, G. and Zhang, L. 2008. miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer. Cancer Biol. Ther. 7, 255-264.   DOI
17 Johnston, R. J. and Hobert, O. 2003. microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature 426, 845-849.   DOI
18 Rhodes, S. D., Wu, X., He, Y., Chen, S., Yang, H., Staser, K. W., Wang, J., Zhang, P., Jiang, C., Yokota, H., Dong, R., Peng, X., Yang, X., Murthy, S., Azhar, M., Mohammad, K. S., Xu, M., Guise, T. A. and Yang, F. C. 2013.Hyperactive transforming growth factor-beta1 signaling potentiates skeletal defects in a neurofibromatosis type 1 mouse model. J. Bone Miner. Res. 28, 2476-2489.   DOI
19 Hua, Z., Lv, Q., Ye, W., Wong, C. K., Cai, G., Gu, D., Ji, Y., Zhao, C., Wang, J., Yang, B. B. and Zhang, Y. 2006. MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One 1, e116.   DOI
20 Huang, X., Le, Q. T. and Giaccia, A. J. 2010. MiR-210-micromanager of the hypoxia pathway. Trends Mol. Med. 16, 230-237.   DOI
21 Kalluri, H. S. and Dempsey, R. J. 2011. IGFBP-3 inhibits the proliferation of neural progenitor cells. Neurochem. Res. 6, 406-411.
22 Uhlmann, S., Zhang, J. D., Schwager, A., Mannsperger, H., Riazalhosseini, Y.,Burmester, S., Ward, A., Korf, U., Wiemann, S. and Sahin, O. 2010. miR-200bc/429 cluster targets PLCgamma1 and differentially regulates proliferation and GF-driven invasion than miR-200a/141 in breast cancer. Oncogene 29, 4297-4306.   DOI
23 Shin, K. K., Kim, Y. S., Kim, J. Y., Bae, Y. C. and Jung, J. S. 2014. miR-137 controls proliferation and differentiation of human adipose tissue stromal cells. Cell. Physiol. Biochem. 33, 758-768.   DOI
24 Tarantino, C., Paolella, G., Cozzuto, L., Minopoli, G., Pastore, L., Parisi, S. and Russo, T. 2010. miRNA 34a, 100, and 137 modulate differentiation of mouse embryonic stem cells. Faseb. J. 24, 3255-3263.   DOI
25 Tsuchiya, S., Fujiwara, T., Sato, F., Shimada, Y., Tanaka, E., Sakai, Y., Shimizu, K. and Tsujimoto, G. 2011. MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1). J. Biol. Chem. 286, 420-428.   DOI
26 Verstappen, G., van Grunsven, L. A., Michiels, C., Van de Putte, T., Souopgui J.,Van Damme, J., Bellefroid, E., Vandekerckhove, J. and Huylebroeck, D. 2008. Atypical Mowat-Wilson patient confirms the importance of the novel association between ZFHX1B/SIP1 and NuRD corepressor complex. Hum. Mol. Genet. 17, 1175-1183.   DOI
27 Wang, Z., Yin, B., Wang, B., Ma, Z., Liu, W. and Lv, G. 2014. MicroRNA-210 promotes proliferation and invasion of peripheral nerve sheath tumor cells targeting EFNA3. Oncol. Res. 21, 145-154.   DOI
28 Kim, Y. J., Bae, S. W., Yu, S. S., Bae, Y. C. and Jung, J. S. 2009. miR-196a regulates proliferation and osteogenic differentiation in mesenchymal stem cells derived from human adipose tissue. J. Bone. Miner. Res. 24, 816-825.   DOI
29 Kamanga-Sollo, E., Pampusch, M. S., Whitem M. E. and Dayton, W. R. 2003. Role of insulin-like growth factor binding protein (IGFBP)-3 in TGF-beta- and GDF-8 (myostatin)- induced suppression of proliferation in porcine embryonic myogenic cell cultures. J. Cell. Physiol. 197, 225-231.   DOI
30 Kim, J. H., Park, S. G., Song, S. Y., Kim, J. K. and Sung, J. H. 2013. Reactive oxygen species-responsive miR-210 regulates proliferation and migration of adipose-derived stem cells via PTPN2. Cell. Death. Dis. 4, e588.   DOI
31 Kim, Y. J., Hwang, S. J., Bae, Y. C. and Jung, J. S. 2009. MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue. Stem Cells 27, 3093-3102.
32 Zeng, L., He, X., Wang, Y., Tang, Y., Zheng, C., Cai, H., Liu, J., Wang, Y., Fu, Y. and Yang, G. Y. 2014. MicroRNA-210 overexpression induces angiogenesis and neurogenesis in the normal adult mouse brain. Gene Ther. 21, 37-43.   DOI
33 Xia, H., Ng, S. S., Jiang, S., Cheung, W. K., Sze, J., Bian, X. W., Kung, H. F. and Lin, M. C. 2010. miR-200a-mediated downregulation of ZEB2 and CTNNB1 differentially inhibits nasopharyngeal carcinoma cell growth, migration and invasion. Biochem. Biophys. Res. Commun. 391, 535-541.   DOI
34 Xu, P., Vernooy, S. Y., Guo, M. and Hay, B. A. 2003. The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr. Biol. 13, 790-795.   DOI
35 Korpal, M., Lee, E. S., Hu, G. and Kang, Y. 2008. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J. Biol. Chem. 283, 14910-14914.   DOI
36 Levi, B., Wan, D. C., Glotzbach, J. P., Hyun, J., Januszyk, M., Montoro, D., Sorkin, M., James, A. W., Nelson, E. R., Li, S., Quarto, N., Lee, M., Gurtner, G. C. and Longaker, M. T. 2011. CD105 protein depletion enhances human adipose- derived stromal cell osteogenesis through reduction of transforming growth factor beta1 (TGF-beta1) signaling. J. Biol. Chem. 286, 39497-39509.   DOI
37 Li, H., Tang, J., Lei, H., Cai, P., Zhu, H., Li, B., Xu, X., Xia, Y. and Tang, W. 2014. Decreased MiR-200a/141 suppress cell migration and proliferation bytargeting PTEN in Hirschsprung's disease. Cell. Physiol. Biochem. 34, 543-553.   DOI
38 Yang, W., Sun, T., Cao, J., Liu, F., Tian, Y. and Zhu, W. 2012. Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro. Exp. Cell Res. 318, 944-954.   DOI
39 Yin, J., Ding, J., Huang, L., Tian, X., Shi, X., Zhi, L., Song, J., Zhang, Y., Gao, X., Yao, Z., Jing, X. and Yang, J. 2013. SND1 affects proliferation of hepatocellular carcinoma cell line SMMC-7721 by regulating IGFBP3 expression. Anat. Rec. (Hoboken) 296, 1568-1575.   DOI
40 Zhang, Z., Sun, H., Dai, H., Walsh, R. M., Imakura, M., Schelter, J., Burchard, J., Dai, X., Chang, A. N., Diaz, R. L., Marszalek, J. R., Bartz, S. R., Carleton, M., Cleary, M. A., Linsley, P. S. and Grandori, C. 2009. MicroRNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT. Cell Cycle 8, 2756-2768.   DOI
41 Zhao, L., Jiang, S. and Hantash, B. M. 2010. Transforming growth factor beta1 induces osteogenic differentiation of murine bone marrow stromal cells. Tissue. Eng. Part. A. 16, 725-733.   DOI
42 Nagaoka, K., Zhang, H., Watanabe, G. and Taya, K. 2013. Epithelial cell differentiation regulated by MicroRNA-200a in mammary glands. PLoS One 8, e65127.   DOI
43 Li, J., Jin, D., Fu, S., Mei, G., Zhou, J., Lei, L., Yu, B. and Wang, G. 2013. Insulin-like growth factor binding protein-3 modulates osteoblast differentiation via interaction with vitamin D receptor. Biochem. Biophys. Res. Commun. 436, 632-637.   DOI
44 Liang, W. C., Wang, Y., Wan, D. C., Yeung, V. S. and Waye, M. M. 2013. Characterization of miR-210 in 3T3-L1 adipogenesis. J. Cell. Biochem. 114, 2699-2707.   DOI
45 Liu, Y., Liu, Q., Jia, W., Chen, J., Wang, J., Ye, D., Guo, X., Chen, W., Li, G., Wang, G., Deng, A. and Kang, J. 2013. MicroRNA-200a regulates Grb2 and suppresses differentiation of mouse embryonic stem cells into endoderm and mesoderm. PLoS One 8, e68990.   DOI
46 Lu, D. F., Yao, Y., Su, Z. Z., Zeng, Z. H., Xing, X. W., He, Z. Y. and Zhang, C. 2014. Downregulation of HDAC1 is involved in the cardiomyocyte differentiation from mesenchymal stem cells in a myocardial microenvironment. PLoS One 9, e93222.   DOI
47 Mizuno, Y., Tokuzawa, Y., Ninomiya, Y., Yagi, K., Yatsuka- Kanesaki, Y., Suda, T., Fukuda, T., Katagiri, T., Kondoh, Y., Amemiya, T., Tashiro, H. and Okazaki, Y. 2009. miR-210 promotes osteoblastic differentiation through inhibition of AcvR1b. FEBS. Lett. 583, 2263-2268.   DOI
48 Ochiai, H., Okada, S., Saito, A., Hoshi, K., Yamashita, H., Takato, T. and Azuma, T. 2012. Inhibition of insulin-like growth factor-1 (IGF-1) expression by prolonged transforming growth factor-beta1 (TGF-beta1) administration suppresses osteoblast differentiation. J. Biol. Chem. 287, 22654-22661.   DOI