Skip to main content
Top
Published in: Endocrine 2/2015

01-03-2015 | Original Article

Down-regulation of miR-144 promotes thyroid cancer cell invasion by targeting ZEB1 and ZEB2

Authors: Hongyu Guan, Weiwei Liang, Zhiwei Xie, Hai Li, Juan Liu, Liehua Liu, Lingling Xiu, Yanbing Li

Published in: Endocrine | Issue 2/2015

Login to get access

Abstract

Thyroid cancer is the most common endocrine malignancy, and its incidence has increased rapidly worldwide. The molecular mechanisms underlying thyroid cancer tumorigenesis still need to be further investigated. MicroRNAs (miRNAs), short RNA molecules of approximately 22 nucleotides in length, play crucial roles in tumorigenesis. In the present study, we found that the expression of miR-144 was significantly down-regulated in thyroid cancer as compared with that in normal thyroid tissues, suggesting that miR-144 may be involved in thyroid cancer tumorigenesis. Moreover, our results showed that restoration of miR-144 in K1 and WRO thyroid cancer cells could suppress the invasion and migration capability of these cells. We also demonstrated that miR-144 suppressed the expression of ZEB1 and ZEB2, two E-cadherin suppressors, by directly binding to their 3′-untranslated regions. Furthermore, restoration of ZEB1 or ZEB2 partially rescued the miR-144-induced inhibition of cell invasion. These data suggest miR-144 function as a tumor suppressor in thyroid cancer.
Literature
1.
3.
go back to reference V.V. Vasko, M. Saji, Molecular mechanisms involved in differentiated thyroid cancer invasion and metastasis. Curr. Opin. Oncol. 19, 11–17 (2007)CrossRefPubMed V.V. Vasko, M. Saji, Molecular mechanisms involved in differentiated thyroid cancer invasion and metastasis. Curr. Opin. Oncol. 19, 11–17 (2007)CrossRefPubMed
4.
go back to reference Q. Yang, M. Ji, H. Guan, B. Shi, P. Hou, Shikonin inhibits thyroid cancer cell growth and invasiveness through targeting major signaling pathways. J. Clin. Endocrinol. Metab. 98, E1909–E1917 (2013)CrossRefPubMed Q. Yang, M. Ji, H. Guan, B. Shi, P. Hou, Shikonin inhibits thyroid cancer cell growth and invasiveness through targeting major signaling pathways. J. Clin. Endocrinol. Metab. 98, E1909–E1917 (2013)CrossRefPubMed
6.
go back to reference X.S. Ke, C.M. Liu, D.P. Liu, C.C. Liang, Micrornas: key participants in gene regulatory networks. Curr. Opin. Chem. Biol. 7, 516–523 (2003)CrossRefPubMed X.S. Ke, C.M. Liu, D.P. Liu, C.C. Liang, Micrornas: key participants in gene regulatory networks. Curr. Opin. Chem. Biol. 7, 516–523 (2003)CrossRefPubMed
7.
8.
10.
go back to reference H. He, K. Jazdzewski, W. Li, S. Liyanarachchi, R. Nagy, S. Volinia, G.A. Calin, C.G. Liu, K. Franssila, S. Suster, R.T. Kloos, C.M. Croce, A. de la Chapelle, The role of microrna genes in papillary thyroid carcinoma. Proc. Natl. Acad. Sci. USA 102, 19075–19080 (2005)CrossRefPubMedCentralPubMed H. He, K. Jazdzewski, W. Li, S. Liyanarachchi, R. Nagy, S. Volinia, G.A. Calin, C.G. Liu, K. Franssila, S. Suster, R.T. Kloos, C.M. Croce, A. de la Chapelle, The role of microrna genes in papillary thyroid carcinoma. Proc. Natl. Acad. Sci. USA 102, 19075–19080 (2005)CrossRefPubMedCentralPubMed
11.
go back to reference J.C. Ricarte-Filho, C.S. Fuziwara, A.S. Yamashita, E. Rezende, M.J. da-Silva, E.T. Kimura, Effects of let-7 microrna on cell growth and differentiation of papillary thyroid cancer. Transl. Oncol. 2, 236–241 (2009)CrossRefPubMedCentralPubMed J.C. Ricarte-Filho, C.S. Fuziwara, A.S. Yamashita, E. Rezende, M.J. da-Silva, E.T. Kimura, Effects of let-7 microrna on cell growth and differentiation of papillary thyroid cancer. Transl. Oncol. 2, 236–241 (2009)CrossRefPubMedCentralPubMed
12.
go back to reference H.M. Namlos, L.A. Meza-Zepeda, T. Baroy, I.H. Ostensen, S.H. Kresse, M.L. Kuijjer, M. Serra, H. Burger, A.M. Cleton-Jansen, O. Myklebost, Modulation of the osteosarcoma expression phenotype by micrornas. PLoS One 7, e48086 (2012)CrossRefPubMedCentralPubMed H.M. Namlos, L.A. Meza-Zepeda, T. Baroy, I.H. Ostensen, S.H. Kresse, M.L. Kuijjer, M. Serra, H. Burger, A.M. Cleton-Jansen, O. Myklebost, Modulation of the osteosarcoma expression phenotype by micrornas. PLoS One 7, e48086 (2012)CrossRefPubMedCentralPubMed
13.
go back to reference M. Guled, L. Lahti, P.M. Lindholm, K. Salmenkivi, I. Bagwan, A.G. Nicholson, S. Knuutila, Cdkn2a, nf2, and jun are dysregulated among other genes by mirnas in malignant mesothelioma-a mirna microarray analysis. Genes Chromosome Cancer 48, 615–623 (2009)CrossRef M. Guled, L. Lahti, P.M. Lindholm, K. Salmenkivi, I. Bagwan, A.G. Nicholson, S. Knuutila, Cdkn2a, nf2, and jun are dysregulated among other genes by mirnas in malignant mesothelioma-a mirna microarray analysis. Genes Chromosome Cancer 48, 615–623 (2009)CrossRef
14.
go back to reference S. Akiyoshi, T. Fukagawa, H. Ueo, M. Ishibashi, Y. Takahashi, M. Fabbri, M. Sasako, Y. Maehara, K. Mimori, M. Mori, Clinical significance of mir-144-zfx axis in disseminated tumour cells in bone marrow in gastric cancer cases. Br. J. Cancer 107, 1345–1353 (2012)CrossRefPubMedCentralPubMed S. Akiyoshi, T. Fukagawa, H. Ueo, M. Ishibashi, Y. Takahashi, M. Fabbri, M. Sasako, Y. Maehara, K. Mimori, M. Mori, Clinical significance of mir-144-zfx axis in disseminated tumour cells in bone marrow in gastric cancer cases. Br. J. Cancer 107, 1345–1353 (2012)CrossRefPubMedCentralPubMed
15.
go back to reference S.M. Sureban, R. May, F.G. Mondalek, D. Qu, S. Ponnurangam, P. Pantazis, S. Anant, R.P. Ramanujam, C.W. Houchen, Nanoparticle-based delivery of sidcamkl-1 increases microrna-144 and inhibits colorectal cancer tumor growth via a notch-1 dependent mechanism. J. Nanobiotechnol. 9, 40 (2011)CrossRef S.M. Sureban, R. May, F.G. Mondalek, D. Qu, S. Ponnurangam, P. Pantazis, S. Anant, R.P. Ramanujam, C.W. Houchen, Nanoparticle-based delivery of sidcamkl-1 increases microrna-144 and inhibits colorectal cancer tumor growth via a notch-1 dependent mechanism. J. Nanobiotechnol. 9, 40 (2011)CrossRef
16.
go back to reference L.Y. Zhang, V. Ho-Fun Lee, A.M. Wong, D.L. Kwong, Y.H. Zhu, S.S. Dong, K.L. Kong, J. Chen, S.W. Tsao, X.Y. Guan, L. Fu, Microrna-144 promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma through repression of pten. Carcinogenesis 34, 454–463 (2013)CrossRefPubMed L.Y. Zhang, V. Ho-Fun Lee, A.M. Wong, D.L. Kwong, Y.H. Zhu, S.S. Dong, K.L. Kong, J. Chen, S.W. Tsao, X.Y. Guan, L. Fu, Microrna-144 promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma through repression of pten. Carcinogenesis 34, 454–463 (2013)CrossRefPubMed
17.
go back to reference S. Cahill, P. Smyth, K. Denning, R. Flavin, J. Li, A. Potratz, S.M. Guenther, R. Henfrey, J.J. O’Leary, O. Sheils, Effect of brafv600e mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model. Mol. Cancer 6, 21 (2007)CrossRefPubMedCentralPubMed S. Cahill, P. Smyth, K. Denning, R. Flavin, J. Li, A. Potratz, S.M. Guenther, R. Henfrey, J.J. O’Leary, O. Sheils, Effect of brafv600e mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model. Mol. Cancer 6, 21 (2007)CrossRefPubMedCentralPubMed
18.
go back to reference M. Rossing, R. Borup, R. Henao, O. Winther, J. Vikesaa, O. Niazi, C. Godballe, A. Krogdahl, M. Glud, C. Hjort-Sorensen, K. Kiss, F.N. Bennedbaek, F.C. Nielsen, Down-regulation of micrornas controlling tumourigenic factors in follicular thyroid carcinoma. J. Mol. Endocrinol. 48, 11–23 (2012)CrossRefPubMed M. Rossing, R. Borup, R. Henao, O. Winther, J. Vikesaa, O. Niazi, C. Godballe, A. Krogdahl, M. Glud, C. Hjort-Sorensen, K. Kiss, F.N. Bennedbaek, F.C. Nielsen, Down-regulation of micrornas controlling tumourigenic factors in follicular thyroid carcinoma. J. Mol. Endocrinol. 48, 11–23 (2012)CrossRefPubMed
19.
go back to reference M. Swierniak, A. Wojcicka, M. Czetwertynska, E. Stachlewska, M. Maciag, W. Wiechno, B. Gornicka, M. Bogdanska, L. Koperski, A. de la Chapelle, K. Jazdzewski, In-depth characterization of the microrna transcriptome in normal thyroid and papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 98, E1401–E1409 (2013)CrossRefPubMed M. Swierniak, A. Wojcicka, M. Czetwertynska, E. Stachlewska, M. Maciag, W. Wiechno, B. Gornicka, M. Bogdanska, L. Koperski, A. de la Chapelle, K. Jazdzewski, In-depth characterization of the microrna transcriptome in normal thyroid and papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 98, E1401–E1409 (2013)CrossRefPubMed
20.
21.
go back to reference E.M. Hurt, J.N. Saykally, B.M. Anose, K.R. Kalli, M.M. Sanders, Expression of the zeb1 (deltaef1) transcription factor in human: additional insights. Mol. Cell. Biochem. 318, 89–99 (2008)CrossRefPubMed E.M. Hurt, J.N. Saykally, B.M. Anose, K.R. Kalli, M.M. Sanders, Expression of the zeb1 (deltaef1) transcription factor in human: additional insights. Mol. Cell. Biochem. 318, 89–99 (2008)CrossRefPubMed
22.
go back to reference J. Comijn, G. Berx, P. Vermassen, K. Verschueren, L. van Grunsven, E. Bruyneel, M. Mareel, D. Huylebroeck, F. van Roy, The two-handed e box binding zinc finger protein sip1 downregulates e-cadherin and induces invasion. Mol. Cell 7, 1267–1278 (2001)CrossRefPubMed J. Comijn, G. Berx, P. Vermassen, K. Verschueren, L. van Grunsven, E. Bruyneel, M. Mareel, D. Huylebroeck, F. van Roy, The two-handed e box binding zinc finger protein sip1 downregulates e-cadherin and induces invasion. Mol. Cell 7, 1267–1278 (2001)CrossRefPubMed
23.
go back to reference K. Aigner, L. Descovich, M. Mikula, A. Sultan, B. Dampier, S. Bonne, F. van Roy, W. Mikulits, M. Schreiber, T. Brabletz, W. Sommergruber, N. Schweifer, A. Wernitznig, H. Beug, R. Foisner, A. Eger, The transcription factor zeb1 (deltaef1) represses plakophilin 3 during human cancer progression. FEBS Lett. 581, 1617–1624 (2007)CrossRefPubMedCentralPubMed K. Aigner, L. Descovich, M. Mikula, A. Sultan, B. Dampier, S. Bonne, F. van Roy, W. Mikulits, M. Schreiber, T. Brabletz, W. Sommergruber, N. Schweifer, A. Wernitznig, H. Beug, R. Foisner, A. Eger, The transcription factor zeb1 (deltaef1) represses plakophilin 3 during human cancer progression. FEBS Lett. 581, 1617–1624 (2007)CrossRefPubMedCentralPubMed
24.
go back to reference T.R. Graham, H.E. Zhau, V.A. Odero-Marah, A.O. Osunkoya, K.S. Kimbro, M. Tighiouart, T. Liu, J.W. Simons, R.M. O’Regan, Insulin-like growth factor-i-dependent up-regulation of zeb1 drives epithelial-to-mesenchymal transition in human prostate cancer cells. Cancer Res. 68, 2479–2488 (2008)CrossRefPubMed T.R. Graham, H.E. Zhau, V.A. Odero-Marah, A.O. Osunkoya, K.S. Kimbro, M. Tighiouart, T. Liu, J.W. Simons, R.M. O’Regan, Insulin-like growth factor-i-dependent up-regulation of zeb1 drives epithelial-to-mesenchymal transition in human prostate cancer cells. Cancer Res. 68, 2479–2488 (2008)CrossRefPubMed
25.
go back to reference S. Spaderna, O. Schmalhofer, F. Hlubek, G. Berx, A. Eger, S. Merkel, A. Jung, T. Kirchner, T. Brabletz, A transient, emt-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer. Gastroenterology 131, 830–840 (2006)CrossRefPubMed S. Spaderna, O. Schmalhofer, F. Hlubek, G. Berx, A. Eger, S. Merkel, A. Jung, T. Kirchner, T. Brabletz, A transient, emt-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer. Gastroenterology 131, 830–840 (2006)CrossRefPubMed
26.
go back to reference U. Wellner, J. Schubert, U.C. Burk, O. Schmalhofer, F. Zhu, A. Sonntag, B. Waldvogel, C. Vannier, D. Darling, A. Zur Hausen, V.G. Brunton, J. Morton, O. Sansom, J. Schuler, M.P. Stemmler, C. Herzberger, U. Hopt, T. Keck, S. Brabletz, T. Brabletz, The emt-activator zeb1 promotes tumorigenicity by repressing stemness-inhibiting micrornas. Nat. Cell Biol. 11, 1487–1495 (2009)CrossRefPubMed U. Wellner, J. Schubert, U.C. Burk, O. Schmalhofer, F. Zhu, A. Sonntag, B. Waldvogel, C. Vannier, D. Darling, A. Zur Hausen, V.G. Brunton, J. Morton, O. Sansom, J. Schuler, M.P. Stemmler, C. Herzberger, U. Hopt, T. Keck, S. Brabletz, T. Brabletz, The emt-activator zeb1 promotes tumorigenicity by repressing stemness-inhibiting micrornas. Nat. Cell Biol. 11, 1487–1495 (2009)CrossRefPubMed
27.
go back to reference H. Guan, G. Wei, J. Wu, D. Fang, Z. Liao, H. Xiao, M. Li, Y. Li, Down-regulation of mir-218-2 and its host gene slit3 cooperate to promote invasion and progression of thyroid cancer. J. Clin. Endocrinol. Metab. 98, E1334–E1344 (2013)CrossRefPubMed H. Guan, G. Wei, J. Wu, D. Fang, Z. Liao, H. Xiao, M. Li, Y. Li, Down-regulation of mir-218-2 and its host gene slit3 cooperate to promote invasion and progression of thyroid cancer. J. Clin. Endocrinol. Metab. 98, E1334–E1344 (2013)CrossRefPubMed
28.
go back to reference Cancer Genome Atlas Research, Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061–1068 (2008)CrossRef Cancer Genome Atlas Research, Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061–1068 (2008)CrossRef
29.
go back to reference B.P. Lewis, C.B. Burge, D.P. Bartel, Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microrna targets. Cell 120, 15–20 (2005)CrossRefPubMed B.P. Lewis, C.B. Burge, D.P. Bartel, Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microrna targets. Cell 120, 15–20 (2005)CrossRefPubMed
31.
go back to reference J. Hou, L. Lin, W. Zhou, Z. Wang, G. Ding, Q. Dong, L. Qin, X. Wu, Y. Zheng, Y. Yang, W. Tian, Q. Zhang, C. Wang, Q. Zhang, S.M. Zhuang, L. Zheng, A. Liang, W. Tao, X. Cao, Identification of mirnomes in human liver and hepatocellular carcinoma reveals mir-199a/b-3p as therapeutic target for hepatocellular carcinoma. Cancer Cell 19, 232–243 (2011)CrossRefPubMed J. Hou, L. Lin, W. Zhou, Z. Wang, G. Ding, Q. Dong, L. Qin, X. Wu, Y. Zheng, Y. Yang, W. Tian, Q. Zhang, C. Wang, Q. Zhang, S.M. Zhuang, L. Zheng, A. Liang, W. Tao, X. Cao, Identification of mirnomes in human liver and hepatocellular carcinoma reveals mir-199a/b-3p as therapeutic target for hepatocellular carcinoma. Cancer Cell 19, 232–243 (2011)CrossRefPubMed
32.
go back to reference T. Iwaya, T. Yokobori, N. Nishida, R. Kogo, T. Sudo, F. Tanaka, K. Shibata, G. Sawada, Y. Takahashi, M. Ishibashi, G. Wakabayashi, M. Mori, K. Mimori, Downregulation of mir-144 is associated with colorectal cancer progression via activation of mtor signaling pathway. Carcinogenesis 33, 2391–2397 (2012)CrossRefPubMed T. Iwaya, T. Yokobori, N. Nishida, R. Kogo, T. Sudo, F. Tanaka, K. Shibata, G. Sawada, Y. Takahashi, M. Ishibashi, G. Wakabayashi, M. Mori, K. Mimori, Downregulation of mir-144 is associated with colorectal cancer progression via activation of mtor signaling pathway. Carcinogenesis 33, 2391–2397 (2012)CrossRefPubMed
33.
go back to reference Y. Guo, L. Ying, Y. Tian, P. Yang, Y. Zhu, Z. Wang, F. Qiu, J. Lin, Mir-144 downregulation increases bladder cancer cell proliferation by targeting EZH2 and regulating Wnt signaling. FEBS J. 280, 4531–4538 (2013)CrossRefPubMed Y. Guo, L. Ying, Y. Tian, P. Yang, Y. Zhu, Z. Wang, F. Qiu, J. Lin, Mir-144 downregulation increases bladder cancer cell proliferation by targeting EZH2 and regulating Wnt signaling. FEBS J. 280, 4531–4538 (2013)CrossRefPubMed
34.
go back to reference S.M. Park, A.B. Gaur, E. Lengyel, M.E. Peter, 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 (2008)CrossRefPubMedCentralPubMed S.M. Park, A.B. Gaur, E. Lengyel, M.E. Peter, 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 (2008)CrossRefPubMedCentralPubMed
35.
go back to reference Y. Arima, H. Hayashi, M. Sasaki, M. Hosonaga, T.M. Goto, T. Chiyoda, S. Kuninaka, T. Shibata, H. Ohata, H. Nakagama, Y. Taya, H. Saya, Induction of zeb proteins by inactivation of rb protein is key determinant of mesenchymal phenotype of breast cancer. J. Biol. Chem. 287, 7896–7906 (2012)CrossRefPubMedCentralPubMed Y. Arima, H. Hayashi, M. Sasaki, M. Hosonaga, T.M. Goto, T. Chiyoda, S. Kuninaka, T. Shibata, H. Ohata, H. Nakagama, Y. Taya, H. Saya, Induction of zeb proteins by inactivation of rb protein is key determinant of mesenchymal phenotype of breast cancer. J. Biol. Chem. 287, 7896–7906 (2012)CrossRefPubMedCentralPubMed
36.
go back to reference J. Braun, C. Hoang-Vu, H. Dralle, S. Huttelmaier, Downregulation of micrornas directs the emt and invasive potential of anaplastic thyroid carcinomas. Oncogene 29, 4237–4244 (2010)CrossRefPubMed J. Braun, C. Hoang-Vu, H. Dralle, S. Huttelmaier, Downregulation of micrornas directs the emt and invasive potential of anaplastic thyroid carcinomas. Oncogene 29, 4237–4244 (2010)CrossRefPubMed
37.
go back to reference A. Hebrant, G. Dom, M. Dewaele, G. Andry, C. Tresallet, E. Leteurtre, J.E. Dumont, C. Maenhaut, mrna expression in papillary and anaplastic thyroid carcinoma: molecular anatomy of a killing switch. PLoS One 7, e37807 (2012)CrossRefPubMedCentralPubMed A. Hebrant, G. Dom, M. Dewaele, G. Andry, C. Tresallet, E. Leteurtre, J.E. Dumont, C. Maenhaut, mrna expression in papillary and anaplastic thyroid carcinoma: molecular anatomy of a killing switch. PLoS One 7, e37807 (2012)CrossRefPubMedCentralPubMed
38.
go back to reference C. Montemayor-Garcia, H. Hardin, Z. Guo, C. Larrain, D. Buehler, S. Asioli, H. Chen, R.V. Lloyd, The role of epithelial mesenchymal transition markers in thyroid carcinoma progression. Endocr. Pathol. 24, 206–212 (2013)CrossRefPubMed C. Montemayor-Garcia, H. Hardin, Z. Guo, C. Larrain, D. Buehler, S. Asioli, H. Chen, R.V. Lloyd, The role of epithelial mesenchymal transition markers in thyroid carcinoma progression. Endocr. Pathol. 24, 206–212 (2013)CrossRefPubMed
39.
go back to reference F. De Amicis, A. Perri, D. Vizza, A. Russo, M.L. Panno, D. Bonofiglio, C. Giordano, L. Mauro, S. Aquila, D. Tramontano, S. Ando, Epigallocatechin gallate inhibits growth and epithelial-to-mesenchymal transition in human thyroid carcinoma cell lines. J. Cell. Physiol. 228, 2054–2062 (2013)CrossRefPubMed F. De Amicis, A. Perri, D. Vizza, A. Russo, M.L. Panno, D. Bonofiglio, C. Giordano, L. Mauro, S. Aquila, D. Tramontano, S. Ando, Epigallocatechin gallate inhibits growth and epithelial-to-mesenchymal transition in human thyroid carcinoma cell lines. J. Cell. Physiol. 228, 2054–2062 (2013)CrossRefPubMed
40.
go back to reference X. Meng, D.H. Kong, N. Li, Z.H. Zong, B.Q. Liu, Z.X. Du, Y. Guan, L. Cao, H.Q. Wang, Knockdown of bag3 induces epithelial-mesenchymal transition in thyroid cancer cells through zeb1 activation. Cell Death Dis. 5, e1092 (2014)CrossRefPubMedCentralPubMed X. Meng, D.H. Kong, N. Li, Z.H. Zong, B.Q. Liu, Z.X. Du, Y. Guan, L. Cao, H.Q. Wang, Knockdown of bag3 induces epithelial-mesenchymal transition in thyroid cancer cells through zeb1 activation. Cell Death Dis. 5, e1092 (2014)CrossRefPubMedCentralPubMed
Metadata
Title
Down-regulation of miR-144 promotes thyroid cancer cell invasion by targeting ZEB1 and ZEB2
Authors
Hongyu Guan
Weiwei Liang
Zhiwei Xie
Hai Li
Juan Liu
Liehua Liu
Lingling Xiu
Yanbing Li
Publication date
01-03-2015
Publisher
Springer US
Published in
Endocrine / Issue 2/2015
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-014-0326-7

Other articles of this Issue 2/2015

Endocrine 2/2015 Go to the issue