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Erschienen in: Journal of Neuro-Oncology 1/2014

01.05.2014 | Laboratory Investigation

Expression of PRMT5 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth in vitro

verfasst von: Xiaosi Han, Rong Li, Wenbin Zhang, Xiuhua Yang, Crystal G. Wheeler, Gregory K. Friedman, Paula Province, Qiang Ding, Zhiying You, Hassan M. Fathallah-Shaykh, G. Yancey Gillespie, Xinyang Zhao, Peter H. King, L. Burt Nabors

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2014

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Abstract

Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of ω-NG,N′G-symmetric dimethylarginine residues on histones as well as other proteins. These modifications play an important role in cell differentiation and tumor cell growth. However, the role of PRMT5 in human glioma cells has not been characterized. In this study, we assessed protein expression profiles of PRMT5 in control brain, WHO grade II astrocytomas, anaplastic astrocytomas, and glioblastoma multiforme (GBM) by immunohistochemistry. PRMT5 was low in glial cells in control brain tissues and low grade astrocytomas. Its expression increased in parallel with malignant progression, and was highly expressed in GBM. Knockdown of PRMT5 by small hairpin RNA caused alterations of p-ERK1/2 and significantly repressed the clonogenic potential and viability of glioma cells. These findings indicate that PRMT5 is a marker of malignant progression in glioma tumors and plays a pivotal role in tumor growth.
Literatur
1.
Zurück zum Zitat Yang Y, Bedford MT (2013) Protein arginine methyltransferases and cancer. Nat Rev 13(1):37–50CrossRef Yang Y, Bedford MT (2013) Protein arginine methyltransferases and cancer. Nat Rev 13(1):37–50CrossRef
2.
Zurück zum Zitat Friesen WJ, Paushkin S, Wyce A et al (2001) The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins. Mol Cell Biol 21(24):8289–8300PubMedCentralPubMedCrossRef Friesen WJ, Paushkin S, Wyce A et al (2001) The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins. Mol Cell Biol 21(24):8289–8300PubMedCentralPubMedCrossRef
3.
Zurück zum Zitat Hsu JM, Chen CT, Chou CK et al (2011) Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation. Nat Cell Biol 13(2):174–181PubMedCentralPubMedCrossRef Hsu JM, Chen CT, Chou CK et al (2011) Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation. Nat Cell Biol 13(2):174–181PubMedCentralPubMedCrossRef
4.
Zurück zum Zitat Jansson M, Durant ST, Cho EC et al (2008) Arginine methylation regulates the p53 response. Nat Cell Biol 10(12):1431–1439PubMedCrossRef Jansson M, Durant ST, Cho EC et al (2008) Arginine methylation regulates the p53 response. Nat Cell Biol 10(12):1431–1439PubMedCrossRef
5.
Zurück zum Zitat Teng Y, Girvan AC, Casson LK et al (2007) AS1411 alters the localization of a complex containing protein arginine methyltransferase 5 and nucleolin. Cancer Res 67(21):10491–10500PubMedCrossRef Teng Y, Girvan AC, Casson LK et al (2007) AS1411 alters the localization of a complex containing protein arginine methyltransferase 5 and nucleolin. Cancer Res 67(21):10491–10500PubMedCrossRef
6.
Zurück zum Zitat Scoumanne A, Zhang J, Chen X (2009) PRMT5 is required for cell-cycle progression and p53 tumor suppressor function. Nucleic Acids Res 37(15):4965–4976PubMedCentralPubMedCrossRef Scoumanne A, Zhang J, Chen X (2009) PRMT5 is required for cell-cycle progression and p53 tumor suppressor function. Nucleic Acids Res 37(15):4965–4976PubMedCentralPubMedCrossRef
7.
Zurück zum Zitat Andreu-Perez P, Esteve-Puig R, Esteve-Puig R, de Torre-Minguela C et al (2011) Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF. Sci Signal 4(190):ra58PubMedCrossRef Andreu-Perez P, Esteve-Puig R, Esteve-Puig R, de Torre-Minguela C et al (2011) Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF. Sci Signal 4(190):ra58PubMedCrossRef
8.
Zurück zum Zitat Pal S, Baiocchi RA, Byrd JC et al (2007) Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphoma. EMBO J 26(15):3558–3569PubMedCentralPubMedCrossRef Pal S, Baiocchi RA, Byrd JC et al (2007) Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphoma. EMBO J 26(15):3558–3569PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat Wang L, Pal S, Sif S (2008) Protein arginine methyltransferase 5 suppresses the transcription of the RB family of tumor suppressors in leukemia and lymphoma cells. Mol Cell Biol 28(20):6262–6277PubMedCentralPubMedCrossRef Wang L, Pal S, Sif S (2008) Protein arginine methyltransferase 5 suppresses the transcription of the RB family of tumor suppressors in leukemia and lymphoma cells. Mol Cell Biol 28(20):6262–6277PubMedCentralPubMedCrossRef
10.
Zurück zum Zitat Kim JM, Sohn HY, Yoon SY et al (2005) Identification of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells. Clin Cancer Res 11(2 Pt 1):473–482PubMed Kim JM, Sohn HY, Yoon SY et al (2005) Identification of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells. Clin Cancer Res 11(2 Pt 1):473–482PubMed
11.
Zurück zum Zitat Eckert D, Biermann K, Nettersheim D et al (2008) Expression of BLIMP1/PRMT5 and concurrent histone H2A/H4 arginine 3 dimethylation in fetal germ cells, CIS/IGCNU and germ cell tumors. BMC Dev Biol 8:106PubMedCentralPubMedCrossRef Eckert D, Biermann K, Nettersheim D et al (2008) Expression of BLIMP1/PRMT5 and concurrent histone H2A/H4 arginine 3 dimethylation in fetal germ cells, CIS/IGCNU and germ cell tumors. BMC Dev Biol 8:106PubMedCentralPubMedCrossRef
12.
Zurück zum Zitat Powers MA, Fay MM, Factor RE et al (2011) Protein arginine methyltransferase 5 accelerates tumor growth by arginine methylation of the tumor suppressor programmed cell death 4. Cancer Res 71(16):5579–5587PubMedCentralPubMedCrossRef Powers MA, Fay MM, Factor RE et al (2011) Protein arginine methyltransferase 5 accelerates tumor growth by arginine methylation of the tumor suppressor programmed cell death 4. Cancer Res 71(16):5579–5587PubMedCentralPubMedCrossRef
13.
Zurück zum Zitat Bao X, Zhao S, Liu T et al (2013) Overexpression of PRMT5 promotes tumor cell growth and is associated with poor disease prognosis in epithelial ovarian cancer. J Histochem Cytochem 61(3):206–217PubMedCentralPubMedCrossRef Bao X, Zhao S, Liu T et al (2013) Overexpression of PRMT5 promotes tumor cell growth and is associated with poor disease prognosis in epithelial ovarian cancer. J Histochem Cytochem 61(3):206–217PubMedCentralPubMedCrossRef
14.
Zurück zum Zitat Tanaka H, Hoshikawa Y, Oh-hara T et al (2009) PRMT5, a novel TRAIL receptor-binding protein, inhibits TRAIL-induced apoptosis via nuclear factor-kappaB activation. Mol Cancer Res 7(4):557–569PubMedCrossRef Tanaka H, Hoshikawa Y, Oh-hara T et al (2009) PRMT5, a novel TRAIL receptor-binding protein, inhibits TRAIL-induced apoptosis via nuclear factor-kappaB activation. Mol Cancer Res 7(4):557–569PubMedCrossRef
15.
Zurück zum Zitat Yang M, Sun J, Sun X et al (2009) Caenorhabditis elegans protein arginine methyltransferase PRMT-5 negatively regulates DNA damage-induced apoptosis. PLoS Genet 5(6):e1000514PubMedCentralPubMedCrossRef Yang M, Sun J, Sun X et al (2009) Caenorhabditis elegans protein arginine methyltransferase PRMT-5 negatively regulates DNA damage-induced apoptosis. PLoS Genet 5(6):e1000514PubMedCentralPubMedCrossRef
16.
Zurück zum Zitat Aggarwal P, Vaites LP, Kim JK et al (2010) Nuclear cyclin D1/CDK4 kinase regulates CUL4 expression and triggers neoplastic growth via activation of the PRMT5 methyltransferase. Cancer Cell 18(4):329–340PubMedCentralPubMedCrossRef Aggarwal P, Vaites LP, Kim JK et al (2010) Nuclear cyclin D1/CDK4 kinase regulates CUL4 expression and triggers neoplastic growth via activation of the PRMT5 methyltransferase. Cancer Cell 18(4):329–340PubMedCentralPubMedCrossRef
17.
Zurück zum Zitat Pal S, Vishwanath SN, Erdjument-Bromage H, Tempst P, Sif S (2004) Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively regulates expression of ST7 and NM23 tumor suppressor genes. Mol Cell Biol 24(21):9630–9645PubMedCentralPubMedCrossRef Pal S, Vishwanath SN, Erdjument-Bromage H, Tempst P, Sif S (2004) Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively regulates expression of ST7 and NM23 tumor suppressor genes. Mol Cell Biol 24(21):9630–9645PubMedCentralPubMedCrossRef
18.
Zurück zum Zitat Tee WW, Pardo M, Theunissen TW et al (2010) PRMT5 is essential for early mouse development and acts in the cytoplasm to maintain ES cell pluripotency. Genes Dev 24(24):2772–2777PubMedCentralPubMedCrossRef Tee WW, Pardo M, Theunissen TW et al (2010) PRMT5 is essential for early mouse development and acts in the cytoplasm to maintain ES cell pluripotency. Genes Dev 24(24):2772–2777PubMedCentralPubMedCrossRef
19.
20.
Zurück zum Zitat Chittka A, Nitarska J, Grazini U, Richardson WD (2012) Transcription factor positive regulatory domain 4 (PRDM4) recruits protein arginine methyltransferase 5 (PRMT5) to mediate histone arginine methylation and control neural stem cell proliferation and differentiation. J Biol Chem 287(51):42995–43006PubMedCentralPubMedCrossRef Chittka A, Nitarska J, Grazini U, Richardson WD (2012) Transcription factor positive regulatory domain 4 (PRDM4) recruits protein arginine methyltransferase 5 (PRMT5) to mediate histone arginine methylation and control neural stem cell proliferation and differentiation. J Biol Chem 287(51):42995–43006PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Jemal A, Murray T, Samuels A et al (2003) Cancer statistics, 2003. CA Cancer J Clin 53(1):5–26PubMedCrossRef Jemal A, Murray T, Samuels A et al (2003) Cancer statistics, 2003. CA Cancer J Clin 53(1):5–26PubMedCrossRef
22.
Zurück zum Zitat Ohgaki H, Kleihues P (2005) Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 64(6):479–489PubMed Ohgaki H, Kleihues P (2005) Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 64(6):479–489PubMed
23.
Zurück zum Zitat Tran B, Rosenthal MA (2010) Survival comparison between glioblastoma multiforme and other incurable cancers. J Clin Neurosci 17(4):417–421PubMedCrossRef Tran B, Rosenthal MA (2010) Survival comparison between glioblastoma multiforme and other incurable cancers. J Clin Neurosci 17(4):417–421PubMedCrossRef
24.
Zurück zum Zitat Ishibashi H, Suzuki T, Suzuki S et al (2003) Sex steroid hormone receptors in human thymoma. J Clin Endocrinol Metab 88(5):2309–2317PubMedCrossRef Ishibashi H, Suzuki T, Suzuki S et al (2003) Sex steroid hormone receptors in human thymoma. J Clin Endocrinol Metab 88(5):2309–2317PubMedCrossRef
25.
Zurück zum Zitat Robertson D, Savage K, Reis-Filho JS, Isacke CM (2008) Multiple immunofluorescence labelling of formalin-fixed paraffin-embedded (FFPE) tissue. BMC Cell Biol 9:13PubMedCentralPubMedCrossRef Robertson D, Savage K, Reis-Filho JS, Isacke CM (2008) Multiple immunofluorescence labelling of formalin-fixed paraffin-embedded (FFPE) tissue. BMC Cell Biol 9:13PubMedCentralPubMedCrossRef
26.
Zurück zum Zitat Inai T, Mancuso M, Hashizume H et al (2004) Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol 165(1):35–52PubMedCentralPubMedCrossRef Inai T, Mancuso M, Hashizume H et al (2004) Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol 165(1):35–52PubMedCentralPubMedCrossRef
27.
Zurück zum Zitat Wiederschain D, Wee S, Chen L et al (2009) Single-vector inducible lentiviral RNAi system for oncology target validation. Cell Cycle 8(3):498–504PubMedCrossRef Wiederschain D, Wee S, Chen L et al (2009) Single-vector inducible lentiviral RNAi system for oncology target validation. Cell Cycle 8(3):498–504PubMedCrossRef
28.
Zurück zum Zitat Han X, Stewart JE Jr, Bellis SL et al (2001) TGF-beta1 up-regulates paxillin protein expression in malignant astrocytoma cells: requirement for a fibronectin substrate. Oncogene 20(55):7976–7986PubMedCrossRef Han X, Stewart JE Jr, Bellis SL et al (2001) TGF-beta1 up-regulates paxillin protein expression in malignant astrocytoma cells: requirement for a fibronectin substrate. Oncogene 20(55):7976–7986PubMedCrossRef
29.
Zurück zum Zitat Karkhanis V, Hu YJ, Baiocchi RA et al (2011) Versatility of PRMT5-induced methylation in growth control and development. Trends Biochem Sci 36(12):633–641PubMedCentralPubMedCrossRef Karkhanis V, Hu YJ, Baiocchi RA et al (2011) Versatility of PRMT5-induced methylation in growth control and development. Trends Biochem Sci 36(12):633–641PubMedCentralPubMedCrossRef
30.
Zurück zum Zitat Lee JH, Cook JR, Yang ZH et al (2005) PRMT7, a new protein arginine methyltransferase that synthesizes symmetric dimethylarginine. J Biol Chem 280(5):3656–3664PubMedCrossRef Lee JH, Cook JR, Yang ZH et al (2005) PRMT7, a new protein arginine methyltransferase that synthesizes symmetric dimethylarginine. J Biol Chem 280(5):3656–3664PubMedCrossRef
31.
Zurück zum Zitat Zhao Q, Rank G, Tan YT et al (2009) PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing. Nat Struct Mol Biol 16(3):304–311PubMedCrossRef Zhao Q, Rank G, Tan YT et al (2009) PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing. Nat Struct Mol Biol 16(3):304–311PubMedCrossRef
32.
Zurück zum Zitat Ancelin K, Lange UC, Hajkova P et al (2006) Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells. Nat Cell Biol 8(6):623–630PubMedCrossRef Ancelin K, Lange UC, Hajkova P et al (2006) Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells. Nat Cell Biol 8(6):623–630PubMedCrossRef
34.
Zurück zum Zitat Huang J, Vogel G, Yu Z, Almazan G, Richard S (2011) Type II arginine methyltransferase PRMT5 regulates gene expression of inhibitors of differentiation/DNA binding Id2 and Id4 during glial cell differentiation. J Biol Chem 286(52):44424–44432PubMedCentralPubMedCrossRef Huang J, Vogel G, Yu Z, Almazan G, Richard S (2011) Type II arginine methyltransferase PRMT5 regulates gene expression of inhibitors of differentiation/DNA binding Id2 and Id4 during glial cell differentiation. J Biol Chem 286(52):44424–44432PubMedCentralPubMedCrossRef
35.
Zurück zum Zitat Friedmann-Morvinski D, Bushong EA, Ke E et al (2012) Dedifferentiation of neurons and astrocytes by oncogenes can induce gliomas in mice. Science 338(6110):1080–1084PubMedCentralPubMedCrossRef Friedmann-Morvinski D, Bushong EA, Ke E et al (2012) Dedifferentiation of neurons and astrocytes by oncogenes can induce gliomas in mice. Science 338(6110):1080–1084PubMedCentralPubMedCrossRef
36.
37.
Zurück zum Zitat Verhaak RG, Hoadley KA, Purdom E et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17(1):98–110PubMedCentralPubMedCrossRef Verhaak RG, Hoadley KA, Purdom E et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17(1):98–110PubMedCentralPubMedCrossRef
38.
Zurück zum Zitat Krakstad C, Chekenya M (2010) Survival signalling and apoptosis resistance in glioblastomas: opportunities for targeted therapeutics. Mol Cancer 9:135PubMedCentralPubMedCrossRef Krakstad C, Chekenya M (2010) Survival signalling and apoptosis resistance in glioblastomas: opportunities for targeted therapeutics. Mol Cancer 9:135PubMedCentralPubMedCrossRef
39.
Zurück zum Zitat Marshall CJ (1995) Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80(2):179–185PubMedCrossRef Marshall CJ (1995) Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80(2):179–185PubMedCrossRef
40.
Zurück zum Zitat Olsen BB, Svenstrup TH, Guerra B (2012) Downregulation of protein kinase CK2 induces autophagic cell death through modulation of the mTOR and MAPK signaling pathways in human glioblastoma cells. Int J Oncol 41(6):1967–1976PubMedCentralPubMed Olsen BB, Svenstrup TH, Guerra B (2012) Downregulation of protein kinase CK2 induces autophagic cell death through modulation of the mTOR and MAPK signaling pathways in human glioblastoma cells. Int J Oncol 41(6):1967–1976PubMedCentralPubMed
41.
Zurück zum Zitat Pang L, Sawada T, Decker SJ, Saltiel AR (1995) Inhibition of MAP kinase kinase blocks the differentiation of PC-12 cells induced by nerve growth factor. J Biol Chem 270(23):13585–13588PubMedCrossRef Pang L, Sawada T, Decker SJ, Saltiel AR (1995) Inhibition of MAP kinase kinase blocks the differentiation of PC-12 cells induced by nerve growth factor. J Biol Chem 270(23):13585–13588PubMedCrossRef
42.
Zurück zum Zitat Ravi RK, Weber E, McMahon M et al (1998) Activated Raf-1 causes growth arrest in human small cell lung cancer cells. J Clin Investig 101(1):153–159PubMedCentralPubMedCrossRef Ravi RK, Weber E, McMahon M et al (1998) Activated Raf-1 causes growth arrest in human small cell lung cancer cells. J Clin Investig 101(1):153–159PubMedCentralPubMedCrossRef
Metadaten
Titel
Expression of PRMT5 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth in vitro
verfasst von
Xiaosi Han
Rong Li
Wenbin Zhang
Xiuhua Yang
Crystal G. Wheeler
Gregory K. Friedman
Paula Province
Qiang Ding
Zhiying You
Hassan M. Fathallah-Shaykh
G. Yancey Gillespie
Xinyang Zhao
Peter H. King
L. Burt Nabors
Publikationsdatum
01.05.2014
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 1/2014
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-014-1419-0

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