Abstract
OBJECTIVE To observe the effect of phenylacetate on the expression of RNA editing deaminase ADAR2 mRNA in glioma cells.
METHODS Primary glial cells from human brain tissue and glioma U-251MG cells were cultured. The expression of ADAR2 mRNA was detected by a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The levels of ADAR2 mRNA expression before and after treatment with phenylacetate were tested by RT-PCR and image analysis. The level of ADAR2 gene expression was presented as the ratio expression rate (RER) of ADAR2 gene/β-actin based on computer image analysis.
RESULTS The ADAR2 mRNA displayed mild expression in brain glial cells, and a high expression level in high-grade malignant U-251MG glioma cells. Computer image analysis showed that the RERs of the ADAR2 gene in the U-251MG cells before and after treatment with 4.0, and 5.0 mM phenylacetate for 8 h were 100.0, 73.5, 60.3, respectively. The expression of ADAR2 mRNA was decreased by phenylacetate in glioma U-251MG cells.
CONCLUSION Phenylacetate can decrease the expression of ADAR2 mRNA in glioma cells, suggesting that phenylacetate, as a drug, may act on the course of RNA editing in gliomas.
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References
Barlati S, Barbon A. RNA editing: a molecular mechanism for the fine modulation of neuronal transmission. Acta Neurochir Suppl. 2005;93:53–57.
Valente L, Nishikura K. ADAR gene family and A-to-I RNA editing: diverse roles in posttranscriptional gene regulation. Prog Nucleic Acid Res Mol Biol. 2005;79:299–338.
Macbeth MR, Schubert HL, Vandemark AP, et al. Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing. Science. 2005; 309:1534–1539.
Yang W, Wang Q, Howell KL, et al. ADAR1 RNA deaminase limits short interfering RNA efficacy in mammalian cells. J Biol Chem. 2005;280:3946–3953.
Holland EC. Glioblastoma multiforme: The terminator. Proc Natl Acad Sci USA. 2000;97:6242–6244.
Bigner D D, Bigner S H, Ponten J, et al. Heterogeneity of genotypic and phenotypic characteristics of fifteen permanent cell lines derived from human gliomas. J Neuropathol Exp Neurol. 1981;40:201–229.
Maas S, Patt S, Schrey M, et al. Underediting of glutamate receptor GluR-B mRNA in malignant gliomas. Proc Natl Acad Sci USA. 2001;98:14687–14692.
Levanon EY, Eisenberg E, Yelin R, et al. Systematic identification of abundant A-to-I editing sites in the human transcriptome. Nature Biotech. 2004;22:1001–1005.
Sommer B, Kohler M, Sprengel, et al. RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell. 1991;67:11–19.
Paschen W, Hedreen JC, Ross CA. RNA editing of the glutamate receptor subunits GluR2 and GluR6 in human brain tissue. J Neurochem. 1994;63:1596–1602.
Maas S, Rich A. Changing genetic information through RNA editing. Bioessays. 2000;22:790–802.
Palladino MJ, Keegan LP, O’Connell, et al. A-to-I pre-mRNA editing in Drosophila is primarily involved in adult nervous system function and integrity. Cell. 2000;102:437–449.
Wang Q, Khillan J, Gadue P, et al. Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis. Science. 2000;290:1765–1768.
Higuchi M, Maas S, Single FN, et el. Point mutation in an AMPA receptor gene rescues lethality in mice didicient in the RNA-editing enzyme ADAR2. Nature. 2000;406:78–81.
Kallman AM, Sahlin M, Ohman M. ADAR2 A→I editing: site selectivity and editing efficiency are separate events. Nucleic Acids Res. 2003;31:4874–4881.
Chen CX, Cho DS, Wang Q, et al. A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single-and double-stranded RNA binding domains. RNA. 2000;6:755–767.
Li XN, Parikh S, Shu Q, et al. Phenylbutyrate and phenylacetate induce differentiation and inhibit proliferation of human medulloblastoma cells. Clin Cancer Res. 2004;10:1150–1159.
Schmidt F, Groscurth P, Kermer M, et al. Lovastatin and phenylacetate induce apoptosis, but not differentiation, in human malignant glioma cells. Acta Neuropathol (Berl). 2001;101:217–224.
Tian Y, Yang C, Zhao C. Up regulation of phenylacetate to glioma homeobox gene expression. Chin J Oncol. 2002;24:126–128.
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This study was supported by the National Nature Science Foundation of China (No. 30271334).
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Tian, Y., Pan, Y., Gao, Y. et al. Phenylacetate down-regulates expression of RNA editing deaminase ADAR2 mRNA in U-251MG glioma cells. Chin. J. Clin. Oncol. 3, 1–4 (2006). https://doi.org/10.1007/s11805-006-0062-8
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DOI: https://doi.org/10.1007/s11805-006-0062-8