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Published in: Tumor Biology 4/2014

01-04-2014 | Research Article

MicroRNA218 inhibits glioma migration and invasion via inhibiting glioma-associated oncogene homolog 1 expression at N terminus

Authors: Biao Peng, Dan Li, Mingjun Qin, Dongdong Luo, Xun Zhang, Hailin Zhao, Su Hu

Published in: Tumor Biology | Issue 4/2014

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Abstract

Glioma is characterized by high invasion, migration and proliferation abilities. However, the molecular mechanism that triggers the development and recurrence of this tumor is also elusive. This study aims to investigate the biological function and molecular mechanism of microRNA218 in glioma. Human glioma samples were obtained and employed to investigate the correlation between microRNA218 and glioma pathological grading. Glioma cell viability was detected by the cell-counting kit-8 (CCK-8) cell counting assay. Transwell assay and wound-healing assay were employed to examine the migration and invasion of the glioma cells. The mRNA transcription and protein expression of glioma-associated oncogene homolog 1 (GLI1) were analyzed by quantitative RT-PCR and Western blot analysis, respectively. Southwestern blot assay was utilized to explore the possible interaction site of GLI1 and microRNA218. The results indicated that microRNA218 is significantly down-regulated in glioma samples and negatively correlated with the pathological grading. The cell viability was significantly decreased, and migration and invasion were significantly inhibited in microRNA218 treated cells, compared with un-treated cells. GLI1 was discovered acting as a functional downstream target of microRNA218, by which microRNA218 inhibited glioma cell migration and invasion. Southwestern blot result showed that microRNA218 targeted directly the N terminus of GLI1 molecular, and repressed the GLI1 expression in U87MG cells. In conclusion, microRNA218 could reduce the invasion and migration, and inhibit proliferation of glioma cells by suppressing the expression of GLI1 protein at the interacting with the N terminus.
Literature
2.
go back to reference Tu YY, Gao XC, Li G. MicroRNA-218 inhibits glioma invasion, migration, proliferation and cancer stem-like cell self-renewal by targeting the polycomb group gene Bmi1. Cancer Res. 2013. doi:10.1158/0008-5472.CAN-13-0358. Tu YY, Gao XC, Li G. MicroRNA-218 inhibits glioma invasion, migration, proliferation and cancer stem-like cell self-renewal by targeting the polycomb group gene Bmi1. Cancer Res. 2013. doi:10.​1158/​0008-5472.​CAN-13-0358.
3.
go back to reference Ohgaki H, Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 2005;64(6):479–89.PubMed Ohgaki H, Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 2005;64(6):479–89.PubMed
4.
go back to reference Louis DN, Ohgaki H, Wiestler QD, Gavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumors of the central nervous system. Acta Neuropathol. 2007;114(2):97–109.PubMedCentralPubMedCrossRef Louis DN, Ohgaki H, Wiestler QD, Gavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumors of the central nervous system. Acta Neuropathol. 2007;114(2):97–109.PubMedCentralPubMedCrossRef
5.
go back to reference Koga Y, Yasunaga M, Moriya Y, Akasu T, Fujita S, Yamamoto S, et al. Exosome can prevent RNase from degrading microRNA in fece. J Gastrointest Oncol. 2011;2(4):215–22.PubMedCentralPubMed Koga Y, Yasunaga M, Moriya Y, Akasu T, Fujita S, Yamamoto S, et al. Exosome can prevent RNase from degrading microRNA in fece. J Gastrointest Oncol. 2011;2(4):215–22.PubMedCentralPubMed
6.
go back to reference Li YY, Wang Y, Yu L, Sun CY, Cheng DG, Yu SZ, et al. miR-146b-5p inhibits glioma migration and invasion by targeting MMP16. Cancer Lett. 2013;339(2):260–9.PubMedCrossRef Li YY, Wang Y, Yu L, Sun CY, Cheng DG, Yu SZ, et al. miR-146b-5p inhibits glioma migration and invasion by targeting MMP16. Cancer Lett. 2013;339(2):260–9.PubMedCrossRef
7.
go back to reference Lu S, Mukkada VA, Mangray S, Cleveland K, Shillingford N, Schorl C, et al. MicroRNA profiling in mucosal biopsies of eosinophilic esophagitis patients pre and post-treatment with steroids with relationship with mRNA targets. PLoS One. 2012;7(7):e40676.PubMedCentralPubMedCrossRef Lu S, Mukkada VA, Mangray S, Cleveland K, Shillingford N, Schorl C, et al. MicroRNA profiling in mucosal biopsies of eosinophilic esophagitis patients pre and post-treatment with steroids with relationship with mRNA targets. PLoS One. 2012;7(7):e40676.PubMedCentralPubMedCrossRef
9.
go back to reference Li QJ, Zhou L, Yang F, Wang GX, Zheng H, Wang DS, et al. MicroRNA-10b promotes migration and invasion through CADM1 in human hepatocellular carcinoma cells. Tumor Biol. 2012;33(5):1455–65.CrossRef Li QJ, Zhou L, Yang F, Wang GX, Zheng H, Wang DS, et al. MicroRNA-10b promotes migration and invasion through CADM1 in human hepatocellular carcinoma cells. Tumor Biol. 2012;33(5):1455–65.CrossRef
10.
go back to reference Sana J, Hajduch M, Michalek J, Vyzula R, Slaby O. MicroRNA and glioblastoma: roles in core signaling pathways and potential clinical implications. J Cell Mol Med. 2011;15(8):1636–44.PubMedCrossRef Sana J, Hajduch M, Michalek J, Vyzula R, Slaby O. MicroRNA and glioblastoma: roles in core signaling pathways and potential clinical implications. J Cell Mol Med. 2011;15(8):1636–44.PubMedCrossRef
11.
go back to reference Garcia AI, Buisson M, Bertrand P, Rimokh R, Rouleau E, Lopez BS, et al. Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers. EMBO Mol Med. 2011;3(5):279–90.PubMedCentralPubMedCrossRef Garcia AI, Buisson M, Bertrand P, Rimokh R, Rouleau E, Lopez BS, et al. Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers. EMBO Mol Med. 2011;3(5):279–90.PubMedCentralPubMedCrossRef
13.
go back to reference Skalsky RL, Cullen BR. Reduced expression of brain-enriched microRNA in glioblastomas permits targeted regulation of a cell death gene. PLoS One. 2011;6(9):e24248.PubMedCentralPubMedCrossRef Skalsky RL, Cullen BR. Reduced expression of brain-enriched microRNA in glioblastomas permits targeted regulation of a cell death gene. PLoS One. 2011;6(9):e24248.PubMedCentralPubMedCrossRef
14.
go back to reference Song L, Huang Q, Chen K, Liu L, Lin C, Dai T, et al. miR-218 inhibits the invasive ability of glioma cells by direct downregulation of IKK-beta. Biochem Biophys Res Commun. 2010;402(1):135–40.PubMedCrossRef Song L, Huang Q, Chen K, Liu L, Lin C, Dai T, et al. miR-218 inhibits the invasive ability of glioma cells by direct downregulation of IKK-beta. Biochem Biophys Res Commun. 2010;402(1):135–40.PubMedCrossRef
15.
go back to reference Li CH, To KF, Tong JHM, Xiao ZG, Xia T, Lai PBS, et al. Enhancer of zeste homolog 2 silences microRNA-218 in human pancreatic ductal adenocarcinoma cells by inducing formation of heterochromatin. Gastroenterology. 2013;144(5):1086–97.PubMedCrossRef Li CH, To KF, Tong JHM, Xiao ZG, Xia T, Lai PBS, et al. Enhancer of zeste homolog 2 silences microRNA-218 in human pancreatic ductal adenocarcinoma cells by inducing formation of heterochromatin. Gastroenterology. 2013;144(5):1086–97.PubMedCrossRef
16.
go back to reference Yamasaki T, Seki N, Yoshino H, Itesako T, Hidaka H, Yamada Y, et al. MicroRNA-218 inhibits cell migration and invasion in renal cell carcinoma through targeting Caveolin-2 involved in focal adhesion pathway. J Urol. 2013;190(3):1059–68.PubMedCrossRef Yamasaki T, Seki N, Yoshino H, Itesako T, Hidaka H, Yamada Y, et al. MicroRNA-218 inhibits cell migration and invasion in renal cell carcinoma through targeting Caveolin-2 involved in focal adhesion pathway. J Urol. 2013;190(3):1059–68.PubMedCrossRef
18.
go back to reference Lees CW, Zacharias WJ, Tremelling M, Noble CL, Nimmo ER, Tenesa A, et al. Analysis of germline GLI1 variation implicates hedgehog signaling in the regulation of intestinal inflammatory pathways. PLoS Med. 2008;5(12):e239.PubMedCentralPubMedCrossRef Lees CW, Zacharias WJ, Tremelling M, Noble CL, Nimmo ER, Tenesa A, et al. Analysis of germline GLI1 variation implicates hedgehog signaling in the regulation of intestinal inflammatory pathways. PLoS Med. 2008;5(12):e239.PubMedCentralPubMedCrossRef
20.
go back to reference Zhang Y, Dutta A, Abounader R. The role of microRNAs in glioma initiation and progression. Front Biosci (Landmark Ed). 2012;17(1):700–12.CrossRef Zhang Y, Dutta A, Abounader R. The role of microRNAs in glioma initiation and progression. Front Biosci (Landmark Ed). 2012;17(1):700–12.CrossRef
21.
go back to reference Malzkorn B, Wolter M, Liesenberg F, Grzendowski M, Stuhler K, Meyer HE, et al. Identification and functional characterization of microRNAs involved in the malignant progression of gliomas. Brain Pathol. 2010;20(3):539–50.PubMedCrossRef Malzkorn B, Wolter M, Liesenberg F, Grzendowski M, Stuhler K, Meyer HE, et al. Identification and functional characterization of microRNAs involved in the malignant progression of gliomas. Brain Pathol. 2010;20(3):539–50.PubMedCrossRef
22.
go back to reference Gaur A, Jewell DA, Liang Y, Ridzon D, Moore JH, Chen C, et al. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 2007;67(6):2456–68.PubMedCrossRef Gaur A, Jewell DA, Liang Y, Ridzon D, Moore JH, Chen C, et al. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 2007;67(6):2456–68.PubMedCrossRef
23.
go back to reference Setty M, Helmy K, Khan AA, Silber J, Arvey A, Neezen F, et al. Inferring transcription and microRNA-mediated regulatory programs in gliomastoma. Mol Syst Biol. 2012;8(1):605.PubMedCentralPubMed Setty M, Helmy K, Khan AA, Silber J, Arvey A, Neezen F, et al. Inferring transcription and microRNA-mediated regulatory programs in gliomastoma. Mol Syst Biol. 2012;8(1):605.PubMedCentralPubMed
24.
go back to reference Kasper M, Regl G, Frischauf AM, Aberger F. GLI transcription factors: mediators of oncogenic Hedgehog signaling. Eur J Cancer. 2006;42(4):437–45.PubMedCrossRef Kasper M, Regl G, Frischauf AM, Aberger F. GLI transcription factors: mediators of oncogenic Hedgehog signaling. Eur J Cancer. 2006;42(4):437–45.PubMedCrossRef
25.
go back to reference Nisson M, Unden AB, Krause D, Malmqwist U, Raza K, Zaphiropoulos PG, et al. Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1. Proc Natl Acad Sci U S A. 2000;97(7):3438–43.CrossRef Nisson M, Unden AB, Krause D, Malmqwist U, Raza K, Zaphiropoulos PG, et al. Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1. Proc Natl Acad Sci U S A. 2000;97(7):3438–43.CrossRef
26.
go back to reference Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruizi AA. HEDGEHOG-GLI1 signaling regulates human growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol. 2007;17(2):165–72.PubMedCentralPubMedCrossRef Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruizi AA. HEDGEHOG-GLI1 signaling regulates human growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol. 2007;17(2):165–72.PubMedCentralPubMedCrossRef
27.
go back to reference Ruizi Altaba A, Mas C, Stecca B. The GLI code: an information nexus regulating cell fate, stemness and cancer. Trends Cell Biol. 2007;17(9):438–47.CrossRef Ruizi Altaba A, Mas C, Stecca B. The GLI code: an information nexus regulating cell fate, stemness and cancer. Trends Cell Biol. 2007;17(9):438–47.CrossRef
28.
go back to reference Agarwal NK, Qu C, Kunkalla K, Liu Y, Vega F. Transcriptional regulation of serine/threonine protein kinase (AKT) genes by glioma-associated oncogene homolog 1. J Biol Chem. 2013;288(21):15390–401.PubMedCrossRef Agarwal NK, Qu C, Kunkalla K, Liu Y, Vega F. Transcriptional regulation of serine/threonine protein kinase (AKT) genes by glioma-associated oncogene homolog 1. J Biol Chem. 2013;288(21):15390–401.PubMedCrossRef
29.
go back to reference Shimakawa T, Tostar U, Lauth M, Palaniswamy R, Kasper M, Toftgard R, et al. Novel human Glioma-associated oncogene 1 (GLI1) splice variants reveal distinct mechanism in the terminal teransduction of the hedgehog signal. J Biol Chem. 2008;283(21):14345–54.CrossRef Shimakawa T, Tostar U, Lauth M, Palaniswamy R, Kasper M, Toftgard R, et al. Novel human Glioma-associated oncogene 1 (GLI1) splice variants reveal distinct mechanism in the terminal teransduction of the hedgehog signal. J Biol Chem. 2008;283(21):14345–54.CrossRef
Metadata
Title
MicroRNA218 inhibits glioma migration and invasion via inhibiting glioma-associated oncogene homolog 1 expression at N terminus
Authors
Biao Peng
Dan Li
Mingjun Qin
Dongdong Luo
Xun Zhang
Hailin Zhao
Su Hu
Publication date
01-04-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1507-3

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