Skip to main content
Top
Published in: Journal of Neuro-Oncology 3/2013

01-12-2013 | Laboratory Investigation

MicroRNA-9 inhibits vasculogenic mimicry of glioma cell lines by suppressing Stathmin expression

Authors: Yuwen Song, Luyan Mu, Xuezhe Han, Qingla Li, Baijing Dong, Hulun Li, Xiaoqian Liu

Published in: Journal of Neuro-Oncology | Issue 3/2013

Login to get access

Abstract

The purpose of this study was to investigate the functions of microRNA-9, which is a tissue-specific microRNA in central nervous system, in the vasculogenic mimicry (VM) of glioma cell lines in vitro and in vivo.Glioma cell lines U87MG, U251 and SHG44 were transfected with microRNA-9 mimic, microRNA-9 inhibitor or scramble sequences. The amount of microRNA-9 and Stathmin (STMN1) mRNA was determined by quantitative real-time PCR, and the protein expression of STMN1 was determined by western blot. Cell proliferation and apoptosis were assessed. The interactions between the 3′UTR of STMN1 and miR-9 was determined by luciferase reporter assay. The VM capacity in vitro was evaluated using VM formation assay, and the rescue experiment of STMN1 was carried out in U251 cells. The in vivo experiment was applied with animal models implanted with U87MG cells.MicroRNA-9 mimic transfection reduced proliferation and increased apoptosis in glioma cell lines (p < 0.05). MicroRNA-9 mimic up-regulated STMN1 mRNA levels but reduced its protein levels (p < 0.05), and luciferase activity of STMN1 was suppressed by microRNA-9 mimic transfection (p < 0.05). Furthermore, microRNA-9 mimic transfection suppressed tumor volume growth, as well as VM both in vitro and in vivo. The cell viability and microtube density were upregulated in U251 cells after STMN1 up-regulation (p < 0.05). STMN1 is a target of microRNA-9, and microRNA-9 could modulate cell proliferation, VM and tumor volume growth through controlling STMN1 expression. MicroRNA-9 and its targets may represent a novel panel of molecules for the development of glioma treatment.
Appendix
Available only for authorised users
Literature
1.
go back to reference Rubin CI, Atweh GF (2004) The role of Stathmin in the regulation of the cell cycle. J Cell Biochem 93:242–250PubMedCrossRef Rubin CI, Atweh GF (2004) The role of Stathmin in the regulation of the cell cycle. J Cell Biochem 93:242–250PubMedCrossRef
2.
go back to reference Bhat KM, Setaluri V (2007) Microtubule-associated proteins as targets in cancer chemotherapy. Clin Cancer Res 13:2849–2854PubMedCrossRef Bhat KM, Setaluri V (2007) Microtubule-associated proteins as targets in cancer chemotherapy. Clin Cancer Res 13:2849–2854PubMedCrossRef
3.
go back to reference Leibl S, Zigeuner R, Hutterer G et al (2008) EGFR expression in urothelial carcinoma of the upper urinary tract is associated with disease progression and metaplastic morphology. APMIS 116:27–32PubMedCrossRef Leibl S, Zigeuner R, Hutterer G et al (2008) EGFR expression in urothelial carcinoma of the upper urinary tract is associated with disease progression and metaplastic morphology. APMIS 116:27–32PubMedCrossRef
4.
go back to reference Cassimeris L (2002) The oncoprotein 18/Stathmin family of microtubule destabilizers. Curr Opin Cell Biol 14:18–24PubMedCrossRef Cassimeris L (2002) The oncoprotein 18/Stathmin family of microtubule destabilizers. Curr Opin Cell Biol 14:18–24PubMedCrossRef
5.
go back to reference Rana S, Maples PB, Senzer N et al (2008) Stathmin 1: a novel therapeutic target for anticancer activity. Expert Rev Anticancer Ther 8:1461–1470PubMedCrossRef Rana S, Maples PB, Senzer N et al (2008) Stathmin 1: a novel therapeutic target for anticancer activity. Expert Rev Anticancer Ther 8:1461–1470PubMedCrossRef
6.
go back to reference Dong B, Mu L, Qin X et al (2012) Stathmin expression in glioma-derived microvascular endothelial cells: a novel therapeutic target. Oncol Rep 27:714–718PubMed Dong B, Mu L, Qin X et al (2012) Stathmin expression in glioma-derived microvascular endothelial cells: a novel therapeutic target. Oncol Rep 27:714–718PubMed
7.
go back to reference Iorio MV, Croce CM (2009) MicroRNAs in cancer: small molecules with a huge impact. J Clin Oncol 27:5848–5856PubMedCrossRef Iorio MV, Croce CM (2009) MicroRNAs in cancer: small molecules with a huge impact. J Clin Oncol 27:5848–5856PubMedCrossRef
8.
go back to reference Omura N, Li CP, Li A, Hong SM et al (2008) Genome-wide profiling of methylated promoters in pancreatic adenocarcinoma. Cancer Biol Ther 7:1146–1156PubMedCrossRef Omura N, Li CP, Li A, Hong SM et al (2008) Genome-wide profiling of methylated promoters in pancreatic adenocarcinoma. Cancer Biol Ther 7:1146–1156PubMedCrossRef
9.
go back to reference Bandres E, Agirre X, Bitarte N et al (2009) Epigenetic regulation of microRNA expression in colorectal cancer. Int J Cancer 125:2737–2743PubMedCrossRef Bandres E, Agirre X, Bitarte N et al (2009) Epigenetic regulation of microRNA expression in colorectal cancer. Int J Cancer 125:2737–2743PubMedCrossRef
10.
go back to reference Hildebrandt MA, Gu J, Lin J et al (2010) Hsa-miR-9 methylation status is associated with cancer development and metastatic recurrence in patients with clear cell renal cell carcinoma. Oncogene 29:5724–5728PubMedCrossRef Hildebrandt MA, Gu J, Lin J et al (2010) Hsa-miR-9 methylation status is associated with cancer development and metastatic recurrence in patients with clear cell renal cell carcinoma. Oncogene 29:5724–5728PubMedCrossRef
11.
go back to reference Krichevsky AM, King KS, Donachue CP et al (2003) A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9:1274–1281PubMedCrossRef Krichevsky AM, King KS, Donachue CP et al (2003) A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9:1274–1281PubMedCrossRef
12.
go back to reference Krichevsky AM, Sonntag KC, Isacson O et al (2006) Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells 24:857–864PubMedCrossRef Krichevsky AM, Sonntag KC, Isacson O et al (2006) Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells 24:857–864PubMedCrossRef
13.
go back to reference Delaloy C, Gao FB (2010) A new role for microRNA-9 in human progenitor cells. Cell Cycle 15:2913–2914CrossRef Delaloy C, Gao FB (2010) A new role for microRNA-9 in human progenitor cells. Cell Cycle 15:2913–2914CrossRef
14.
go back to reference Delaloy C, Liu L, Lee JA et al (2010) MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors. Cell Stem Cell 4:323–335CrossRef Delaloy C, Liu L, Lee JA et al (2010) MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors. Cell Stem Cell 4:323–335CrossRef
15.
go back to reference Shibata M, Kurokawa D, Nakao H et al (2008) MicroRNA-9 #odulates Cajal-Retzius cell differentiation by suppressing Foxg1 expression in mouse medial pallium. J Neurosci 41:10415–10421CrossRef Shibata M, Kurokawa D, Nakao H et al (2008) MicroRNA-9 #odulates Cajal-Retzius cell differentiation by suppressing Foxg1 expression in mouse medial pallium. J Neurosci 41:10415–10421CrossRef
16.
go back to reference Li Y, Wang F, Lee JA et al (2006) MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila. Gene Dev 20:2793–2805PubMedCrossRef Li Y, Wang F, Lee JA et al (2006) MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila. Gene Dev 20:2793–2805PubMedCrossRef
17.
go back to reference Otaegi G, Pollock A, Hong J et al (2011) MicroRNA miR-9 modifies motor neuron columns by a tuning regulation of FoxP1 levels in developing spinal cords. J Neurosci 3:809–818CrossRef Otaegi G, Pollock A, Hong J et al (2011) MicroRNA miR-9 modifies motor neuron columns by a tuning regulation of FoxP1 levels in developing spinal cords. J Neurosci 3:809–818CrossRef
18.
go back to reference Bonev B, Pisco A, Papalopulu N (2011) MicroRNA-9 reveals regional diversity of neural progenitors along the anterior-posterior axis. Dev Cell 1:19–32CrossRef Bonev B, Pisco A, Papalopulu N (2011) MicroRNA-9 reveals regional diversity of neural progenitors along the anterior-posterior axis. Dev Cell 1:19–32CrossRef
19.
go back to reference Holmfeldt P, Sellin ME, Gullberg M (2009) Predominant regulators of tubulin monomer-polymer partitioning and their implication for cell polarization. Cell Mol Life Sci 66:3263–3276PubMedCrossRef Holmfeldt P, Sellin ME, Gullberg M (2009) Predominant regulators of tubulin monomer-polymer partitioning and their implication for cell polarization. Cell Mol Life Sci 66:3263–3276PubMedCrossRef
20.
go back to reference Ingber D, Prusty D, Zhengqi S et al (1995) Cell shape, cytoskeletal mechanics and cell cycle control in angiogenesis. J Biomech 28:1471–1484PubMedCrossRef Ingber D, Prusty D, Zhengqi S et al (1995) Cell shape, cytoskeletal mechanics and cell cycle control in angiogenesis. J Biomech 28:1471–1484PubMedCrossRef
21.
go back to reference Petrovic V, Costa RH, Lau LF et al (2008) FoxM1 regulates growth factor-induced expression of kinase-interacting stathmin to promote cell cycle progression. J Biol Chem 283:453–460PubMedCrossRef Petrovic V, Costa RH, Lau LF et al (2008) FoxM1 regulates growth factor-induced expression of kinase-interacting stathmin to promote cell cycle progression. J Biol Chem 283:453–460PubMedCrossRef
22.
go back to reference Kouzu Y, Uzawa K, Koike H et al (2006) Overexpression of Stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis. Br J Cancer 94:717–723PubMed Kouzu Y, Uzawa K, Koike H et al (2006) Overexpression of Stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis. Br J Cancer 94:717–723PubMed
23.
go back to reference Yuan RH, YM J, Chen HL et al (2006) Stathmin overexpression cooperates with p53 mutation and osteopontin overexpression, and is associated with tumour progression, early recurrence, and poor prognosis in hepatocellular carcinoma. J Pathol 209:549–558PubMedCrossRef Yuan RH, YM J, Chen HL et al (2006) Stathmin overexpression cooperates with p53 mutation and osteopontin overexpression, and is associated with tumour progression, early recurrence, and poor prognosis in hepatocellular carcinoma. J Pathol 209:549–558PubMedCrossRef
24.
go back to reference Ghosh R, Gu G, Tillman E et al (2007) Increased expression and differential phosphorylation of stathmin may promote prostate cancer progression. Prostate 67:1038–1052PubMedCrossRef Ghosh R, Gu G, Tillman E et al (2007) Increased expression and differential phosphorylation of stathmin may promote prostate cancer progression. Prostate 67:1038–1052PubMedCrossRef
25.
go back to reference Wang R, Dong K, Lin F et al (2007) Inhibiting proliferation and enhancing chemosensitivity to taxanes in osteosarcoma cells by RNA interference-mediated down- regulation of Stathmin expression. Mol Med 13:567–575PubMedCrossRef Wang R, Dong K, Lin F et al (2007) Inhibiting proliferation and enhancing chemosensitivity to taxanes in osteosarcoma cells by RNA interference-mediated down- regulation of Stathmin expression. Mol Med 13:567–575PubMedCrossRef
26.
go back to reference Alli E, Yang JM, Hait WN (2007) Silencing of Stathmin induces tumor-suppressor function in breast cancer cell lines harboring mutant p53. Oncogene 26:1003–1012PubMedCrossRef Alli E, Yang JM, Hait WN (2007) Silencing of Stathmin induces tumor-suppressor function in breast cancer cell lines harboring mutant p53. Oncogene 26:1003–1012PubMedCrossRef
27.
go back to reference Johnsen JI, Aurelio ON, Kwaja Z et al (2000) p53-mediated negative regulation of Stathmin/Op18 expression is associated with G2/M cell-cycle arrest. Int J Cancer 88:685–691PubMedCrossRef Johnsen JI, Aurelio ON, Kwaja Z et al (2000) p53-mediated negative regulation of Stathmin/Op18 expression is associated with G2/M cell-cycle arrest. Int J Cancer 88:685–691PubMedCrossRef
28.
go back to reference Ngo TT, Peng T, Liang XJ et al (2007) The 1p-encoded protein stathmin and resistance of malignant gliomas to nitrosoureas. J Natl Cancer Inst 99:639–652PubMedCrossRef Ngo TT, Peng T, Liang XJ et al (2007) The 1p-encoded protein stathmin and resistance of malignant gliomas to nitrosoureas. J Natl Cancer Inst 99:639–652PubMedCrossRef
29.
go back to reference Liang XJ, Choi Y, Sackett DL et al (2008) Nitrosoureas inhibit the stathmin-mediated migration and invasion of malignant glioma cells. Cancer Res 68:5267–5272PubMedCrossRef Liang XJ, Choi Y, Sackett DL et al (2008) Nitrosoureas inhibit the stathmin-mediated migration and invasion of malignant glioma cells. Cancer Res 68:5267–5272PubMedCrossRef
30.
go back to reference Wong QW, Lung EW, Law PT et al (2008) MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin 1. Gastroenterology 135:257–269PubMedCrossRef Wong QW, Lung EW, Law PT et al (2008) MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin 1. Gastroenterology 135:257–269PubMedCrossRef
31.
go back to reference Wang J, Gu Z, Ni P et al (2011) NF-kappaB P50/P65 hetero-dimer mediates differential regulation of CD166/ALCAM expression via interaction with micoRNA-9 after serum deprivation, providing evidence for a novel negative auto-regulatory loop. Nucleic Acids Res 15:6440–6455CrossRef Wang J, Gu Z, Ni P et al (2011) NF-kappaB P50/P65 hetero-dimer mediates differential regulation of CD166/ALCAM expression via interaction with micoRNA-9 after serum deprivation, providing evidence for a novel negative auto-regulatory loop. Nucleic Acids Res 15:6440–6455CrossRef
32.
go back to reference Myatt S, Wang J, Monteiro L et al (2010) Definition of microRNAs that repression expression of the tumor suppressor gene FOXO1 in endometrial cancer. Cancer Res 70:367–377PubMedCrossRef Myatt S, Wang J, Monteiro L et al (2010) Definition of microRNAs that repression expression of the tumor suppressor gene FOXO1 in endometrial cancer. Cancer Res 70:367–377PubMedCrossRef
33.
go back to reference Ma L, Young J, Prabhala H et al (2010) miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Mat cell Biol 3:247–256 Ma L, Young J, Prabhala H et al (2010) miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Mat cell Biol 3:247–256
34.
go back to reference Luo H, Zhang H, Zhang Z et al (2009) Down-regulated miR-9 and miR-433 in human gastric carcinoma. J Exp Clin Cancer Res 28:82PubMedCrossRef Luo H, Zhang H, Zhang Z et al (2009) Down-regulated miR-9 and miR-433 in human gastric carcinoma. J Exp Clin Cancer Res 28:82PubMedCrossRef
35.
go back to reference Wan H, Guo L, Liu T et al (2010) Regulation of the transcription factor NF-kB1 by micro RNA-9 in human gastric adenocarcinoma. Mole Cancer 9:16CrossRef Wan H, Guo L, Liu T et al (2010) Regulation of the transcription factor NF-kB1 by micro RNA-9 in human gastric adenocarcinoma. Mole Cancer 9:16CrossRef
36.
go back to reference Laios A, O’Toole S, Flavin R et al (2008) Potential role of miR-9 and miR-223 in recurrent ovarian cancer. Mole Cancer 7:35CrossRef Laios A, O’Toole S, Flavin R et al (2008) Potential role of miR-9 and miR-223 in recurrent ovarian cancer. Mole Cancer 7:35CrossRef
37.
go back to reference Arora H, Qureshi R, Jin S et al (2011) miR-9 and let-7g enhance the sensitivity to ionizing radiation by suppression of NFkappaB1. Exp Mole Med 5:298–304CrossRef Arora H, Qureshi R, Jin S et al (2011) miR-9 and let-7g enhance the sensitivity to ionizing radiation by suppression of NFkappaB1. Exp Mole Med 5:298–304CrossRef
38.
go back to reference Nass D, Rosenwald S, Meiri E et al (2009) MiR-92b and miR-9/9* are specifically expressed in brain primary tumors and can be used to differentiate primary from metastatic brain tumors. Brain Pathol 19:375–383PubMedCrossRef Nass D, Rosenwald S, Meiri E et al (2009) MiR-92b and miR-9/9* are specifically expressed in brain primary tumors and can be used to differentiate primary from metastatic brain tumors. Brain Pathol 19:375–383PubMedCrossRef
39.
go back to reference Jeon H, Sohn Y, Oh S et al (2011) ID4 Imparts chemoresistance and cancer stemness to glioma cells by derepressing miR-9*-mediated suppression of SOX2. Cancer Res 9:3410–3421CrossRef Jeon H, Sohn Y, Oh S et al (2011) ID4 Imparts chemoresistance and cancer stemness to glioma cells by derepressing miR-9*-mediated suppression of SOX2. Cancer Res 9:3410–3421CrossRef
40.
go back to reference Schraivogel D, Weimann L, Beier D et al (2011) CAMTA1 is a novel tumour suppressor regulated by miR-9/9* in glioblastoma stem cells. EMBOJ 20:4309–4322CrossRef Schraivogel D, Weimann L, Beier D et al (2011) CAMTA1 is a novel tumour suppressor regulated by miR-9/9* in glioblastoma stem cells. EMBOJ 20:4309–4322CrossRef
41.
go back to reference Ben-Hamo R, Efroni S (2011) Gene expression and network-based analysis reveals a novel role for hsa-miR-9 and drug control over the p38 network in glioblastoma multiforme progression. Genome Med 3(11):77PubMedCrossRef Ben-Hamo R, Efroni S (2011) Gene expression and network-based analysis reveals a novel role for hsa-miR-9 and drug control over the p38 network in glioblastoma multiforme progression. Genome Med 3(11):77PubMedCrossRef
42.
go back to reference Chao T, Zhang Y, Yan X et al (2008) Mir-9 regulates the expression of CBX7 in Human Glioma. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 30:268–274PubMed Chao T, Zhang Y, Yan X et al (2008) Mir-9 regulates the expression of CBX7 in Human Glioma. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 30:268–274PubMed
43.
go back to reference Maniotis AJ, Folberg R, Hess A et al (1999) Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155:739–752PubMedCrossRef Maniotis AJ, Folberg R, Hess A et al (1999) Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155:739–752PubMedCrossRef
45.
go back to reference Wang S, Yu L, Ling G et al (2012) Vasculogenic mimicry and its clinical significance in medulloblastoma. Cancer Biol Ther 5:341–348 Wang S, Yu L, Ling G et al (2012) Vasculogenic mimicry and its clinical significance in medulloblastoma. Cancer Biol Ther 5:341–348
46.
go back to reference Chen Y, Jing Z, Luo C et al (2012) Vasculogenic mimicry-potential target for glioma therapy: an in vitro and in vivo study. Med Oncol 29:324–331PubMedCrossRef Chen Y, Jing Z, Luo C et al (2012) Vasculogenic mimicry-potential target for glioma therapy: an in vitro and in vivo study. Med Oncol 29:324–331PubMedCrossRef
Metadata
Title
MicroRNA-9 inhibits vasculogenic mimicry of glioma cell lines by suppressing Stathmin expression
Authors
Yuwen Song
Luyan Mu
Xuezhe Han
Qingla Li
Baijing Dong
Hulun Li
Xiaoqian Liu
Publication date
01-12-2013
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 3/2013
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-013-1245-9

Other articles of this Issue 3/2013

Journal of Neuro-Oncology 3/2013 Go to the issue