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Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Review

Function and mechanism of tumor suppressor gene LRRC4/NGL-2

Authors: Peiyao Li, Gang Xu, Guiyuan Li, Minghua Wu

Published in: Molecular Cancer | Issue 1/2014

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Abstract

LRRC4/NGL-2 (Leucine rich repeat containing 4/Netrin-G ligand-2), a relatively specific expressed gene in brain tissue, is a member of the LRRC4/ NGL (netrin-G ligand) family and belongs to the superfamily of LRR proteins. LRRC4/NGL-2 regulates neurite outgrowth and lamina-specific dendritic segmentation, suggesting that LRRC4/NGL-2 is important for the development of the nervous system. In addition, LRRC4/NGL-2 has been identified as a tumor suppressor gene. The overexpression of LRRC4/NGL-2 suppresses glioma cell growth, angiogenesis and invasion through complicated signaling regulation networks. LRRC4/NGL-2 also has the ability to form multiphase loops with miRNA, transcription factors and gene methylation modification; the loss of LRRC4/NGL-2 function may be an important event in multiple biological processes in gliomas. In summary, LRRC4/NGL-2 is a critical gene in the normal development and tumorigenesis of the nervous system.
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Literature
1.
go back to reference Kobe B, Deisenhofer J: The leucine-rich repeat: a versatile binding motif. Trends Biochem Sci. 1994, 19: 415-421. 10.1016/0968-0004(94)90090-6CrossRefPubMed Kobe B, Deisenhofer J: The leucine-rich repeat: a versatile binding motif. Trends Biochem Sci. 1994, 19: 415-421. 10.1016/0968-0004(94)90090-6CrossRefPubMed
2.
go back to reference Kobe B, Kajava AV: The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol. 2001, 11: 725-732. 10.1016/S0959-440X(01)00266-4CrossRefPubMed Kobe B, Kajava AV: The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol. 2001, 11: 725-732. 10.1016/S0959-440X(01)00266-4CrossRefPubMed
3.
go back to reference Dolan J, Walshe K, Alsbury S, Hokamp K, O'Keeffe S, Okafuji T, Miller SF, Tear G, Mitchell KJ: The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns. BMC Genomics. 2007, 8: 320- 10.1186/1471-2164-8-320PubMedCentralCrossRefPubMed Dolan J, Walshe K, Alsbury S, Hokamp K, O'Keeffe S, Okafuji T, Miller SF, Tear G, Mitchell KJ: The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns. BMC Genomics. 2007, 8: 320- 10.1186/1471-2164-8-320PubMedCentralCrossRefPubMed
4.
go back to reference Taguchi A, Wanaka A, Mori T, Matsumoto K, Imai Y, Tagaki T, Tohyama M: Molecular cloning of novel leucine-rich repeat proteins and their expression in the developing mouse nervous system. Brain Res Mol Brain Res. 1996, 35: 31-40. 10.1016/0169-328X(95)00178-UCrossRefPubMed Taguchi A, Wanaka A, Mori T, Matsumoto K, Imai Y, Tagaki T, Tohyama M: Molecular cloning of novel leucine-rich repeat proteins and their expression in the developing mouse nervous system. Brain Res Mol Brain Res. 1996, 35: 31-40. 10.1016/0169-328X(95)00178-UCrossRefPubMed
5.
6.
go back to reference Bando T, Morikawa Y, Hisaoka T, Komori T, Miyajima A, Senba E:Dynamic expression pattern of leucine-rich repeat neuronal protein 4 in the mouse dorsal root ganglia during development. Neurosci Lett. 2013, 548: 73-78.CrossRefPubMed Bando T, Morikawa Y, Hisaoka T, Komori T, Miyajima A, Senba E:Dynamic expression pattern of leucine-rich repeat neuronal protein 4 in the mouse dorsal root ganglia during development. Neurosci Lett. 2013, 548: 73-78.CrossRefPubMed
7.
go back to reference Wang J, Qian J, Dong L, Li X, Tan C, Li J, Zhang B: Identification of LRRC4, a Novel Member of Leucine-rich Repeat (LRR) Superfam ily, and Its Expression Analysis in Brain Tumor. Prog Biochem Biophys. 2002, 29: 233-239. Wang J, Qian J, Dong L, Li X, Tan C, Li J, Zhang B: Identification of LRRC4, a Novel Member of Leucine-rich Repeat (LRR) Superfam ily, and Its Expression Analysis in Brain Tumor. Prog Biochem Biophys. 2002, 29: 233-239.
8.
go back to reference Lin JC, Ho WH, Gurney A, Rosenthal A: The netrin-G1 ligand NGL-1 promotes the outgrowth of thalamocortical axons. Nat Neurosci. 2003, 6: 1270-1276. 10.1038/nn1148CrossRefPubMed Lin JC, Ho WH, Gurney A, Rosenthal A: The netrin-G1 ligand NGL-1 promotes the outgrowth of thalamocortical axons. Nat Neurosci. 2003, 6: 1270-1276. 10.1038/nn1148CrossRefPubMed
9.
go back to reference Kim S, Burette A, Chung HS, Kwon SK, Woo J, Lee HW, Kim K, Kim H, Weinberg RJ, Kim E: NGL family PSD-95-interacting adhesion molecules regulate excitatory synapse formation. Nat Neurosci. 2006, 9: 1294-1301. 10.1038/nn1763CrossRefPubMed Kim S, Burette A, Chung HS, Kwon SK, Woo J, Lee HW, Kim K, Kim H, Weinberg RJ, Kim E: NGL family PSD-95-interacting adhesion molecules regulate excitatory synapse formation. Nat Neurosci. 2006, 9: 1294-1301. 10.1038/nn1763CrossRefPubMed
10.
go back to reference Woo J, Kwon SK, Kim E: The NGL family of leucine-rich repeat-containing synaptic adhesion molecules. Mol Cell Neurosci. 2009, 42: 1-10. 10.1016/j.mcn.2009.05.008CrossRefPubMed Woo J, Kwon SK, Kim E: The NGL family of leucine-rich repeat-containing synaptic adhesion molecules. Mol Cell Neurosci. 2009, 42: 1-10. 10.1016/j.mcn.2009.05.008CrossRefPubMed
11.
go back to reference Gu W, Brodtkorb E, Steinlein OK: LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures. Ann Neurol. 2002, 52: 364-367. 10.1002/ana.10280CrossRefPubMed Gu W, Brodtkorb E, Steinlein OK: LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures. Ann Neurol. 2002, 52: 364-367. 10.1002/ana.10280CrossRefPubMed
12.
go back to reference Ko J, Kim E: Leucine-rich repeat proteins of synapses. J Neurosci Res. 2007, 85: 2824-2832. 10.1002/jnr.21306CrossRefPubMed Ko J, Kim E: Leucine-rich repeat proteins of synapses. J Neurosci Res. 2007, 85: 2824-2832. 10.1002/jnr.21306CrossRefPubMed
13.
go back to reference Zhang Q, Wang J, Fan S, Wang L, Cao L, Tang K, Peng C, Li Z, Li W, Gan K, Liu Z, Li X, Shen S, Li G: Expression and functional characterization of LRRC4, a novel brain-specific member of the LRR superfamily. FEBS Lett. 2005, 579: 3674-3682. 10.1016/j.febslet.2005.05.058CrossRefPubMed Zhang Q, Wang J, Fan S, Wang L, Cao L, Tang K, Peng C, Li Z, Li W, Gan K, Liu Z, Li X, Shen S, Li G: Expression and functional characterization of LRRC4, a novel brain-specific member of the LRR superfamily. FEBS Lett. 2005, 579: 3674-3682. 10.1016/j.febslet.2005.05.058CrossRefPubMed
14.
go back to reference Dan L, Ming-hua W, Qiong C, He H, Chen H, Wei-song L, Xiao-ling L, Gui-yuan L: Preparation of anti-LRRC4 polyclonal antibody and its application in constructing expression profile of human gliomas with different pathological grades. J Cent S Univ (Med Sci). 2007, 32: 373-379. Dan L, Ming-hua W, Qiong C, He H, Chen H, Wei-song L, Xiao-ling L, Gui-yuan L: Preparation of anti-LRRC4 polyclonal antibody and its application in constructing expression profile of human gliomas with different pathological grades. J Cent S Univ (Med Sci). 2007, 32: 373-379.
15.
go back to reference Nishimura-Akiyoshi S, Niimi K, Nakashiba T, Itohara S: Axonal netrin-Gs transneuronally determine lamina-specific subdendritic segments. Proc Natl Acad Sci U S A. 2007, 104: 14801-14806. 10.1073/pnas.0706919104PubMedCentralCrossRefPubMed Nishimura-Akiyoshi S, Niimi K, Nakashiba T, Itohara S: Axonal netrin-Gs transneuronally determine lamina-specific subdendritic segments. Proc Natl Acad Sci U S A. 2007, 104: 14801-14806. 10.1073/pnas.0706919104PubMedCentralCrossRefPubMed
16.
go back to reference Carim-Todd L, Escarceller M, Estivill X, Sumoy L: LRRN6A/LERN1 (leucine-rich repeat neuronal protein 1), a novel gene with enriched expression in limbic system and neocortex. Eur J Neurosci. 2003, 18: 3167-3182. 10.1111/j.1460-9568.2003.03003.xCrossRefPubMed Carim-Todd L, Escarceller M, Estivill X, Sumoy L: LRRN6A/LERN1 (leucine-rich repeat neuronal protein 1), a novel gene with enriched expression in limbic system and neocortex. Eur J Neurosci. 2003, 18: 3167-3182. 10.1111/j.1460-9568.2003.03003.xCrossRefPubMed
17.
go back to reference Kuja-Panula J, Kiiltomaki M, Yamashiro T, Rouhiainen A, Rauvala H: AMIGO, a transmembrane protein implicated in axon tract development, defines a novel protein family with leucine-rich repeats. J Cell Biol. 2003, 160: 963-973. 10.1083/jcb.200209074PubMedCentralCrossRefPubMed Kuja-Panula J, Kiiltomaki M, Yamashiro T, Rouhiainen A, Rauvala H: AMIGO, a transmembrane protein implicated in axon tract development, defines a novel protein family with leucine-rich repeats. J Cell Biol. 2003, 160: 963-973. 10.1083/jcb.200209074PubMedCentralCrossRefPubMed
18.
go back to reference Kwon SK, Woo J, Kim SY, Kim H, Kim E: Trans-synaptic adhesions between netrin-G ligand-3 (NGL-3) and receptor tyrosine phosphatases LAR, protein-tyrosine phosphatase delta (PTPdelta), and PTPsigma via specific domains regulate excitatory synapse formation. J Biol Chem. 2010, 285: 13966-13978. 10.1074/jbc.M109.061127PubMedCentralCrossRefPubMed Kwon SK, Woo J, Kim SY, Kim H, Kim E: Trans-synaptic adhesions between netrin-G ligand-3 (NGL-3) and receptor tyrosine phosphatases LAR, protein-tyrosine phosphatase delta (PTPdelta), and PTPsigma via specific domains regulate excitatory synapse formation. J Biol Chem. 2010, 285: 13966-13978. 10.1074/jbc.M109.061127PubMedCentralCrossRefPubMed
19.
20.
go back to reference Wu M, Huang H, Chen Q, Li D, Zheng Z, Xiong W, Zhou Y, Li X, Zhou M, Lu J, Shen S, Li G: Leucine-rich repeat C4 protein is involved in nervous tissue development and neurite outgrowth, and induction of glioma cell differentiation. Acta Biochim Biophys Sin (Shanghai). 2007, 39: 731-738. 10.1111/j.1745-7270.2007.00338.xCrossRef Wu M, Huang H, Chen Q, Li D, Zheng Z, Xiong W, Zhou Y, Li X, Zhou M, Lu J, Shen S, Li G: Leucine-rich repeat C4 protein is involved in nervous tissue development and neurite outgrowth, and induction of glioma cell differentiation. Acta Biochim Biophys Sin (Shanghai). 2007, 39: 731-738. 10.1111/j.1745-7270.2007.00338.xCrossRef
21.
go back to reference DeNardo LA, de Wit J, Otto-Hitt S, Ghosh A: NGL-2 regulates input-specific synapse development in CA1 pyramidal neurons. Neuron. 2012, 76: 762-775. 10.1016/j.neuron.2012.10.013CrossRefPubMed DeNardo LA, de Wit J, Otto-Hitt S, Ghosh A: NGL-2 regulates input-specific synapse development in CA1 pyramidal neurons. Neuron. 2012, 76: 762-775. 10.1016/j.neuron.2012.10.013CrossRefPubMed
22.
go back to reference Soto F, Watkins KL, Johnson RE, Schottler F, Kerschensteiner D: NGL-2 regulates pathway-specific neurite growth and lamination, synapse formation, and signal transmission in the retina. J Neurosci. 2013, 33: 11949-11959. 10.1523/JNEUROSCI.1521-13.2013PubMedCentralCrossRefPubMed Soto F, Watkins KL, Johnson RE, Schottler F, Kerschensteiner D: NGL-2 regulates pathway-specific neurite growth and lamination, synapse formation, and signal transmission in the retina. J Neurosci. 2013, 33: 11949-11959. 10.1523/JNEUROSCI.1521-13.2013PubMedCentralCrossRefPubMed
23.
go back to reference Woo J, Kwon SK, Choi S, Kim S, Lee JR, Dunah AW, Sheng M, Kim E: Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses. Nat Neurosci. 2009, 12: 428-437. 10.1038/nn.2279CrossRefPubMed Woo J, Kwon SK, Choi S, Kim S, Lee JR, Dunah AW, Sheng M, Kim E: Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses. Nat Neurosci. 2009, 12: 428-437. 10.1038/nn.2279CrossRefPubMed
24.
go back to reference Wu M, Huang C, Gan K, Huang H, Chen Q, Ouyang J, Tang Y, Li X, Yang Y, Zhou H, Zhou Y, Zeng Z, Xiao L, Li D, Tang K, Shen S, Li G: LRRC4, a putative tumor suppressor gene, requires a functional leucine-rich repeat cassette domain to inhibit proliferation of glioma cells in vitro by modulating the extracellular signal-regulated kinase/protein kinase B/nuclear factor-kappaB pathway. Mol Biol Cell. 2006, 17: 3534-3542. 10.1091/mbc.E05-11-1082PubMedCentralCrossRefPubMed Wu M, Huang C, Gan K, Huang H, Chen Q, Ouyang J, Tang Y, Li X, Yang Y, Zhou H, Zhou Y, Zeng Z, Xiao L, Li D, Tang K, Shen S, Li G: LRRC4, a putative tumor suppressor gene, requires a functional leucine-rich repeat cassette domain to inhibit proliferation of glioma cells in vitro by modulating the extracellular signal-regulated kinase/protein kinase B/nuclear factor-kappaB pathway. Mol Biol Cell. 2006, 17: 3534-3542. 10.1091/mbc.E05-11-1082PubMedCentralCrossRefPubMed
25.
go back to reference Xiao L, Tu C, Chen S, Yu Z, Lei Q, Wang Z, Xu G, Wu M, Li G: LRRC4 haplotypes are associated with pituitary adenoma in a Chinese population. Med Oncol. 2014, 31: 888-CrossRefPubMed Xiao L, Tu C, Chen S, Yu Z, Lei Q, Wang Z, Xu G, Wu M, Li G: LRRC4 haplotypes are associated with pituitary adenoma in a Chinese population. Med Oncol. 2014, 31: 888-CrossRefPubMed
26.
go back to reference Zhang QH, Wang LL, Cao L, Peng C, Li XL, Tang K, Li WF, Liao P, Wang JR, Li GY: Study of a novel brain relatively specific gene LRRC4 involved in glioma tumorigenesis suppression using the Tet-on system. Acta Biochim Biophys Sin (Shanghai). 2005, 37: 532-540. 10.1111/j.1745-7270.2005.00079.xCrossRef Zhang QH, Wang LL, Cao L, Peng C, Li XL, Tang K, Li WF, Liao P, Wang JR, Li GY: Study of a novel brain relatively specific gene LRRC4 involved in glioma tumorigenesis suppression using the Tet-on system. Acta Biochim Biophys Sin (Shanghai). 2005, 37: 532-540. 10.1111/j.1745-7270.2005.00079.xCrossRef
27.
go back to reference Zhang QH, Wu MH, Wang LL, Cao L, Tang K, Peng C, Gan K, Li XL, Li GY: Profiling of differentially expressed genes in LRRC4 overexpressed glioblastoma cells by cDNA array. Acta Biochim Biophys Sin (Shanghai). 2005, 37: 680-687. 10.1111/j.1745-7270.2005.00100.xCrossRef Zhang QH, Wu MH, Wang LL, Cao L, Tang K, Peng C, Gan K, Li XL, Li GY: Profiling of differentially expressed genes in LRRC4 overexpressed glioblastoma cells by cDNA array. Acta Biochim Biophys Sin (Shanghai). 2005, 37: 680-687. 10.1111/j.1745-7270.2005.00100.xCrossRef
28.
go back to reference Wu M, Gan K, Huang C, Tang Y, Chen Q, Tang K, Li X, Shen S, Li G: LRRC4 controls in vitro invasion of glioblastoma cells through inhibiting RPTP-zeta expression. J Neurooncol. 2006, 80: 133-142. 10.1007/s11060-006-9173-6CrossRefPubMed Wu M, Gan K, Huang C, Tang Y, Chen Q, Tang K, Li X, Shen S, Li G: LRRC4 controls in vitro invasion of glioblastoma cells through inhibiting RPTP-zeta expression. J Neurooncol. 2006, 80: 133-142. 10.1007/s11060-006-9173-6CrossRefPubMed
29.
go back to reference Wu M, Chen Q, Li D, Li X, Li X, Huang C, Tang Y, Zhou Y, Wang D, Tang K, Cao L, Shen S, Li G: LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP-2 activation by reducing SDF-1 alpha/CXCR4-mediated ERK1/2 and Akt signaling pathways. J Cell Biochem. 2008, 103: 245-255. 10.1002/jcb.21400CrossRefPubMed Wu M, Chen Q, Li D, Li X, Li X, Huang C, Tang Y, Zhou Y, Wang D, Tang K, Cao L, Shen S, Li G: LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP-2 activation by reducing SDF-1 alpha/CXCR4-mediated ERK1/2 and Akt signaling pathways. J Cell Biochem. 2008, 103: 245-255. 10.1002/jcb.21400CrossRefPubMed
30.
go back to reference Wu M, Huang C, Li X, Li X, Gan K, Chen Q, Tang Y, Tang K, Shen S, Li G: LRRC4 inhibits glioblastoma cell proliferation, migration, and angiogenesis by downregulating pleiotropic cytokine expression and responses. J Cell Physiol. 2008, 214: 65-74. 10.1002/jcp.21163CrossRefPubMed Wu M, Huang C, Li X, Li X, Gan K, Chen Q, Tang Y, Tang K, Shen S, Li G: LRRC4 inhibits glioblastoma cell proliferation, migration, and angiogenesis by downregulating pleiotropic cytokine expression and responses. J Cell Physiol. 2008, 214: 65-74. 10.1002/jcp.21163CrossRefPubMed
31.
go back to reference Zhang Z, Li D, Wu M, Xiang B, Wang L, Zhou M, Chen P, Li X, Shen S, Li G: Promoter hypermethylation-mediated inactivation of LRRC4 in gliomas. BMC Mol Biol. 2008, 9: 99- 10.1186/1471-2199-9-99PubMedCentralCrossRefPubMed Zhang Z, Li D, Wu M, Xiang B, Wang L, Zhou M, Chen P, Li X, Shen S, Li G: Promoter hypermethylation-mediated inactivation of LRRC4 in gliomas. BMC Mol Biol. 2008, 9: 99- 10.1186/1471-2199-9-99PubMedCentralCrossRefPubMed
32.
go back to reference Minghua W, Zuping Z, Xiaoping L, Hailin T: Methylation Level of Genes and MiRNA-Mediated Methylation Modification Mechanism In Glioma. Protein Purification and Analysis III - Methods and Applications. 2014, Hong Kong: iConcept Press, 1, Minghua W, Zuping Z, Xiaoping L, Hailin T: Methylation Level of Genes and MiRNA-Mediated Methylation Modification Mechanism In Glioma. Protein Purification and Analysis III - Methods and Applications. 2014, Hong Kong: iConcept Press, 1,
33.
go back to reference Mathupala SP, Mittal S, Guthikonda M, Sloan AE: MicroRNA and brain tumors: a cause and a cure?. DNA Cell Biol. 2007, 26: 301-310. 10.1089/dna.2006.0560PubMedCentralCrossRefPubMed Mathupala SP, Mittal S, Guthikonda M, Sloan AE: MicroRNA and brain tumors: a cause and a cure?. DNA Cell Biol. 2007, 26: 301-310. 10.1089/dna.2006.0560PubMedCentralCrossRefPubMed
34.
go back to reference Zhang L, Liu T, Huang Y, Liu J: microRNA-182 inhibits the proliferation and invasion of human lung adenocarcinoma cells through its effect on human cortical actin-associated protein. Int J Mol Med. 2011, 28: 381-388.PubMed Zhang L, Liu T, Huang Y, Liu J: microRNA-182 inhibits the proliferation and invasion of human lung adenocarcinoma cells through its effect on human cortical actin-associated protein. Int J Mol Med. 2011, 28: 381-388.PubMed
36.
go back to reference Kusenda B, Mraz M, Mayer J, Pospisilova S: MicroRNA biogenesis, functionality and cancer relevance. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006, 150: 205-215. 10.5507/bp.2006.029CrossRefPubMed Kusenda B, Mraz M, Mayer J, Pospisilova S: MicroRNA biogenesis, functionality and cancer relevance. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006, 150: 205-215. 10.5507/bp.2006.029CrossRefPubMed
37.
go back to reference Shi L, Cheng Z, Zhang J, Li R, Zhao P, Fu Z, You Y: hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells. Brain Res. 2008, 1236: 185-193.CrossRefPubMed Shi L, Cheng Z, Zhang J, Li R, Zhao P, Fu Z, You Y: hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells. Brain Res. 2008, 1236: 185-193.CrossRefPubMed
38.
go back to reference Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004, 116: 281-297. 10.1016/S0092-8674(04)00045-5CrossRefPubMed Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004, 116: 281-297. 10.1016/S0092-8674(04)00045-5CrossRefPubMed
39.
go back to reference Nelson PT, Baldwin DA, Kloosterman WP, Kauppinen S, Plasterk RH, Mourelatos Z: RAKE and LNA-ISH reveal microRNA expression and localization in archival human brain. RNA. 2006, 12: 187-191.PubMedCentralCrossRefPubMed Nelson PT, Baldwin DA, Kloosterman WP, Kauppinen S, Plasterk RH, Mourelatos Z: RAKE and LNA-ISH reveal microRNA expression and localization in archival human brain. RNA. 2006, 12: 187-191.PubMedCentralCrossRefPubMed
40.
go back to reference Chan JA, Krichevsky AM, Kosik KS: MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005, 65: 6029-6033. 10.1158/0008-5472.CAN-05-0137CrossRefPubMed Chan JA, Krichevsky AM, Kosik KS: MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005, 65: 6029-6033. 10.1158/0008-5472.CAN-05-0137CrossRefPubMed
41.
go back to reference Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG: Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun. 2005, 334: 1351-1358. 10.1016/j.bbrc.2005.07.030CrossRefPubMed Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG: Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun. 2005, 334: 1351-1358. 10.1016/j.bbrc.2005.07.030CrossRefPubMed
42.
go back to reference Mathupala SP, Guthikonda M, Sloan AE: RNAi based approaches to the treatment of malignant glioma. Technol Cancer Res Treat. 2006, 5: 261-269.PubMed Mathupala SP, Guthikonda M, Sloan AE: RNAi based approaches to the treatment of malignant glioma. Technol Cancer Res Treat. 2006, 5: 261-269.PubMed
43.
go back to reference Tang H, Wang Z, Liu Q, Liu X, Wu M, Li G: Disturbing miR-182 and −381 inhibits BRD7 transcription and glioma growth by directly targeting LRRC4. PLoS One. 2014, 9: e84146- 10.1371/journal.pone.0084146PubMedCentralCrossRefPubMed Tang H, Wang Z, Liu Q, Liu X, Wu M, Li G: Disturbing miR-182 and −381 inhibits BRD7 transcription and glioma growth by directly targeting LRRC4. PLoS One. 2014, 9: e84146- 10.1371/journal.pone.0084146PubMedCentralCrossRefPubMed
44.
go back to reference Tang H, Wang Z, Liu X, Liu Q, Xu G, Li G, Wu M: LRRC4 inhibits glioma cell growth and invasion through a miR-185-dependent pathway. Curr Cancer Drug Targets. 2012, 12: 1032-1042. 10.2174/156800912803251180CrossRefPubMed Tang H, Wang Z, Liu X, Liu Q, Xu G, Li G, Wu M: LRRC4 inhibits glioma cell growth and invasion through a miR-185-dependent pathway. Curr Cancer Drug Targets. 2012, 12: 1032-1042. 10.2174/156800912803251180CrossRefPubMed
45.
go back to reference Tang H, Liu X, Wang Z, She X, Zeng X, Deng M, Liao Q, Guo X, Wang R, Li X, Zeng F, Wu M, Li G: Interaction of hsa-miR-381 and glioma suppressor LRRC4 is involved in glioma growth. Brain Res. 2011, 1390: 21-32.CrossRefPubMed Tang H, Liu X, Wang Z, She X, Zeng X, Deng M, Liao Q, Guo X, Wang R, Li X, Zeng F, Wu M, Li G: Interaction of hsa-miR-381 and glioma suppressor LRRC4 is involved in glioma growth. Brain Res. 2011, 1390: 21-32.CrossRefPubMed
46.
go back to reference Minghua W: Methylomes in Epigenetics and Epigenomics. 2014, Rijeka: InTech, Minghua W: Methylomes in Epigenetics and Epigenomics. 2014, Rijeka: InTech,
47.
go back to reference Ozsolak F, Poling LL, Wang Z, Liu H, Liu XS, Roeder RG, Zhang X, Song JS, Fisher DE: Chromatin structure analyses identify miRNA promoters. Genes Dev. 2008, 22: 3172-3183. 10.1101/gad.1706508PubMedCentralCrossRefPubMed Ozsolak F, Poling LL, Wang Z, Liu H, Liu XS, Roeder RG, Zhang X, Song JS, Fisher DE: Chromatin structure analyses identify miRNA promoters. Genes Dev. 2008, 22: 3172-3183. 10.1101/gad.1706508PubMedCentralCrossRefPubMed
48.
go back to reference Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, Teruya-Feldstein J, Reinhardt F, Onder TT, Valastyan S, Westermann F, Speleman F, Vandesompele J, Weinberg RA: miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010, 12: 247-256.PubMedCentralPubMed Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, Teruya-Feldstein J, Reinhardt F, Onder TT, Valastyan S, Westermann F, Speleman F, Vandesompele J, Weinberg RA: miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010, 12: 247-256.PubMedCentralPubMed
49.
go back to reference Schulte JH, Horn S, Otto T, Samans B, Heukamp LC, Eilers UC, Krause M, Astrahantseff K, Klein-Hitpass L, Buettner R, Schramm A, Christiansen H, Eilers M, Eggert A, Berwanger B: MYCN regulates oncogenic MicroRNAs in neuroblastoma. Int J Cancer. 2008, 122: 699-704. 10.1002/ijc.23153CrossRefPubMed Schulte JH, Horn S, Otto T, Samans B, Heukamp LC, Eilers UC, Krause M, Astrahantseff K, Klein-Hitpass L, Buettner R, Schramm A, Christiansen H, Eilers M, Eggert A, Berwanger B: MYCN regulates oncogenic MicroRNAs in neuroblastoma. Int J Cancer. 2008, 122: 699-704. 10.1002/ijc.23153CrossRefPubMed
50.
go back to reference Gehrke S, Imai Y, Sokol N, Lu B: Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature. 2010, 466: 637-641. 10.1038/nature09191PubMedCentralCrossRefPubMed Gehrke S, Imai Y, Sokol N, Lu B: Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature. 2010, 466: 637-641. 10.1038/nature09191PubMedCentralCrossRefPubMed
51.
go back to reference Brock M, Trenkmann M, Gay RE, Michel BA, Gay S, Fischler M, Ulrich S, Speich R, Huber LC: Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway. Circ Res. 2009, 104: 1184-1191. 10.1161/CIRCRESAHA.109.197491CrossRefPubMed Brock M, Trenkmann M, Gay RE, Michel BA, Gay S, Fischler M, Ulrich S, Speich R, Huber LC: Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway. Circ Res. 2009, 104: 1184-1191. 10.1161/CIRCRESAHA.109.197491CrossRefPubMed
52.
go back to reference Rosa A, Brivanlou AH: A regulatory circuitry comprised of miR-302 and the transcription factors OCT4 and NR2F2 regulates human embryonic stem cell differentiation. EMBO J. 2011, 30: 237-248. 10.1038/emboj.2010.319PubMedCentralCrossRefPubMed Rosa A, Brivanlou AH: A regulatory circuitry comprised of miR-302 and the transcription factors OCT4 and NR2F2 regulates human embryonic stem cell differentiation. EMBO J. 2011, 30: 237-248. 10.1038/emboj.2010.319PubMedCentralCrossRefPubMed
53.
go back to reference Brabletz S, Bajdak K, Meidhof S, Burk U, Niedermann G, Firat E, Wellner U, Dimmler A, Faller G, Schubert J, Brabletz T: The ZEB1/miR-200 feedback loop controls Notch signalling in cancer cells. EMBO J. 2011, 30: 770-782. 10.1038/emboj.2010.349PubMedCentralCrossRefPubMed Brabletz S, Bajdak K, Meidhof S, Burk U, Niedermann G, Firat E, Wellner U, Dimmler A, Faller G, Schubert J, Brabletz T: The ZEB1/miR-200 feedback loop controls Notch signalling in cancer cells. EMBO J. 2011, 30: 770-782. 10.1038/emboj.2010.349PubMedCentralCrossRefPubMed
54.
go back to reference Liu S, Wu LC, Pang J, Santhanam R, Schwind S, Wu YZ, Hickey CJ, Yu J, Becker H, Maharry K, Radmacher MD, Li C, Whitman SP, Mishra A, Stauffer N, Eiring AM, Briesewitz R, Baiocchi RA, Chan KK, Paschka P, Caligiuri MA, Byrd JC, Croce CM, Bloomfield CD, Perrotti D, Garzon R, Marcucci G: Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia. Cancer Cell. 2010, 17: 333-347. 10.1016/j.ccr.2010.03.008PubMedCentralCrossRefPubMed Liu S, Wu LC, Pang J, Santhanam R, Schwind S, Wu YZ, Hickey CJ, Yu J, Becker H, Maharry K, Radmacher MD, Li C, Whitman SP, Mishra A, Stauffer N, Eiring AM, Briesewitz R, Baiocchi RA, Chan KK, Paschka P, Caligiuri MA, Byrd JC, Croce CM, Bloomfield CD, Perrotti D, Garzon R, Marcucci G: Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia. Cancer Cell. 2010, 17: 333-347. 10.1016/j.ccr.2010.03.008PubMedCentralCrossRefPubMed
55.
go back to reference Das S, Foley N, Bryan K, Watters KM, Bray I, Murphy DM, Buckley PG, Stallings RL: MicroRNA mediates DNA demethylation events triggered by retinoic acid during neuroblastoma cell differentiation. Cancer Res. 2010, 70: 7874-7881. 10.1158/0008-5472.CAN-10-1534PubMedCentralCrossRefPubMed Das S, Foley N, Bryan K, Watters KM, Bray I, Murphy DM, Buckley PG, Stallings RL: MicroRNA mediates DNA demethylation events triggered by retinoic acid during neuroblastoma cell differentiation. Cancer Res. 2010, 70: 7874-7881. 10.1158/0008-5472.CAN-10-1534PubMedCentralCrossRefPubMed
56.
go back to reference Pan W, Zhu S, Yuan M, Cui H, Wang L, Luo X, Li J, Zhou H, Tang Y, Shen N: MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol. 2010, 184: 6773-6781. 10.4049/jimmunol.0904060CrossRefPubMed Pan W, Zhu S, Yuan M, Cui H, Wang L, Luo X, Li J, Zhou H, Tang Y, Shen N: MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol. 2010, 184: 6773-6781. 10.4049/jimmunol.0904060CrossRefPubMed
57.
go back to reference Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J, Yu J, Muthusamy N, Havelange V, Volinia S, Blum W, Rush LJ, Perrotti D, Andreeff M, Bloomfield CD, Byrd JC, Chan K, Wu LC, Croce CM, Marcucci G: MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood. 2009, 113: 6411-6418. 10.1182/blood-2008-07-170589PubMedCentralCrossRefPubMed Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J, Yu J, Muthusamy N, Havelange V, Volinia S, Blum W, Rush LJ, Perrotti D, Andreeff M, Bloomfield CD, Byrd JC, Chan K, Wu LC, Croce CM, Marcucci G: MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood. 2009, 113: 6411-6418. 10.1182/blood-2008-07-170589PubMedCentralCrossRefPubMed
58.
59.
go back to reference Grady WM, Parkin RK, Mitchell PS, Lee JH, Kim YH, Tsuchiya KD, Washington MK, Paraskeva C, Willson JK, Kaz AM, Kroh EM, Allen A, Fritz BR, Markowitz SD, Tewari M: Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer. Oncogene. 2008, 27: 3880-3888. 10.1038/onc.2008.10CrossRefPubMed Grady WM, Parkin RK, Mitchell PS, Lee JH, Kim YH, Tsuchiya KD, Washington MK, Paraskeva C, Willson JK, Kaz AM, Kroh EM, Allen A, Fritz BR, Markowitz SD, Tewari M: Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer. Oncogene. 2008, 27: 3880-3888. 10.1038/onc.2008.10CrossRefPubMed
60.
go back to reference Lujambio A, Calin GA, Villanueva A, Ropero S, Sanchez-Cespedes M, Blanco D, Montuenga LM, Rossi S, Nicoloso MS, Faller WJ, Gallagher WM, Eccles SA, Croce CM, Esteller M: A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci U S A. 2008, 105: 13556-13561. 10.1073/pnas.0803055105PubMedCentralCrossRefPubMed Lujambio A, Calin GA, Villanueva A, Ropero S, Sanchez-Cespedes M, Blanco D, Montuenga LM, Rossi S, Nicoloso MS, Faller WJ, Gallagher WM, Eccles SA, Croce CM, Esteller M: A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci U S A. 2008, 105: 13556-13561. 10.1073/pnas.0803055105PubMedCentralCrossRefPubMed
Metadata
Title
Function and mechanism of tumor suppressor gene LRRC4/NGL-2
Authors
Peiyao Li
Gang Xu
Guiyuan Li
Minghua Wu
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-266

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