Abnormal expression of an ADAR2 alternative splicing variant in gliomas downregulates adenosine-to-inosine RNA editing

详细信息    查看全文

• 作者：Jun Wei (1)
  Zhaohui Li (1)
  Chao Du (1)
  Bin Qi (2)
  Xingli Zhao (1)
  Liping Wang (3)
  Lirong Bi (4)
  Guan Wang (1)
  Xuan Zhang (5)
  Xiaoyun Su (6)
  Yuzhuo Pan (7)
  Yu Tian (1)
  
• 关键词：Glioma ; ADAR2 ; Self ; editing ; ASVs
• 刊名：Acta Neurochirurgica
• 出版年：2014
• 出版时间：June 2014
• 年：2014
• 卷：156
• 期：6
• 页码：1135-1142
• 全文大小：
• 参考文献：1. Agranat L, Sperling J, Sperling R (2010) A novel tissue-specific alternatively spliced form of the A-to-I RNA editing enzyme ADAR2. RNA Biol 7:253-62 CrossRef
  2. Athanasiadis A, Rich A, Maas S (2004) Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. PLoS Biol 2:e391 CrossRef
  3. Bahn JH, Lee JH, Li G, Greer C, Peng GD, Xiao XS (2012) Accurate identification of A-to-I RNA editing in human by transcriptome sequencing. Genome Research 22:142-50 CrossRef
  4. Buonerba C, Di Lorenzo G, Marinelli A, Federico P, Palmieri G, Imbimbo M, Conti P, Peluso G, De Placido S, Sampson JH (2010) A comprehensive outlook on intra- cerebral therapy of malignant gliomas. Crit Rev Oncol Hematol 80:54-8 CrossRef
  5. Cenci C, Barzotti R, Galeano F, Corbelli S, Rota R, Massimi L, Di Rocco C, O’Connell MA, Gallo A (2008) Downregulation of RNA editing in pediatric astrocytomas: ADAR2 editing activity inhibits cell migration and proliferation. J Biol Chem 283:7251-260 CrossRef
  6. Chin L, Gray JW (2008) Translating insights from the cancer genome into clinical practice. Nature 452:553-63 CrossRef
  7. Dominissini D, Moshitch-Moshkovitz S, Amariglio N, Rechavi G (2011) Adenosine-to-inosine RNA editing meets cancer. Carcinogenesis 32:1569-577 CrossRef
  8. Eisenberg E, Li JB, Levanon EY (2010) Sequence based identification of RNA editing sites. RNA Biol 7:248-52 CrossRef
  9. Galeano F, Leroy A, Rossetti C, Gromova I, Gautier P, Keegan LP, Massimi L, Di Rocco C, O’Connell MA, Gallo A (2010) Human BLCAP transcript: new editing events in normal and cancerous tissues. Int J Cancer 127:127-37 CrossRef
  10. Galeano F, Rossetti C, Tomaselli S, Cifaldi L, Lezzerini M, Pezzullo M, Boldrini R, Massimi L, Rocco CD, Locatelli F, Gallo A (2013) ADAR2-editing activity inhibits glioblastoma growth through the modulation of the CDC14B/Skp2/p21/p27 axis. Oncogene 32:998-009 CrossRef
  11. Galeano F, Tomaselli S, Locatelli F, Gallo A (2012) A-to-I RNA editing: The “ADAR-side of human cancer. Semin Cell Dev Biol 23:244-50 CrossRef
  12. Gallo A, Galardi S (2008) A-to-I RNA editing and cancer: from pathology to basic science. RNA Biol 5:135-39 CrossRef
  13. Gallo A, Locatelli F (2012) ADARs: allies or enemies? The importance of A-to-I RNA editing in human disease: from cancer to HIV-1. Biol Rev Camb Philos Soc 87:95-10 CrossRef
  14. Gurkanlar D, Er U, Sanli M, Ozkan M, Sekerci Z (2005) Peritumoral brain edema in intracranial meningiomas. J Clin Neurosci 12:750-53 CrossRef
  15. Hoelzinger DB, Mariani L, Weis J, Woyke T, Berens TJ, McDonough WS, Sloan A, Coons SW, Berens ME (2005) Gene expression profile of glioblastoma multiforme invasive phenotype points to new therapeutic targets. Neoplasia 7:7-6 CrossRef
  16. Ishiuchi S, Yoshida Y, Sugawara K, Aihara M, Ohtani T, Watanabe T, Saito N, Tsuzuki K, Okado H, Miwa A, Nakazato Y, Ozawa S (2007) Ca 2+ permeable AMPA receptors regulate growth of human glioblastoma via Akt activation. J Neurosci 27:7987-001 CrossRef
  17. Jacobs MM, Fogg RL, Emeson RB, Stanwood GD (2009) ADAR1 and ADAR2 expression and editing activity during forebrain development. Dev Neurosci 31:223-37 CrossRef
  18. Kawahara Y, Ito K, Ito M, Tsuji S, Kwak S (2005) Novel splice variants of human ADAR2 mRNA: Skipping of the exon encoding the dsRNA-binding domains, and multiple C-terminal splice sites. Gene 22:193-01 CrossRef
  19. Li M, Wang IX, Li Y, Bruzel A, Richards AL, Toung JM, Cheung VG (2011) Widespread RNA and DNA Sequence Differences in the Human Transcriptome. Science 333:53-8 CrossRef
  20. Maas S, Gommans WM (2009) Novel exon of mammalian ADAR2 extends open reading frame. PLoS One 4:e4225 CrossRef
  21. Maas S, Kawahara Y, Tamburro KM, Nishikura K (2006) A-to-I RNA editing and human disease. RNA Biol 3:1- CrossRef
  22. Maas S, Patt S, Schrey M, Rich A (2001) Underediting of glutamate receptor GluR-B mRNA in malignant gliomas. Proc Natl Acad Sci USA 98:14687-4692 CrossRef
  23. Mittaz L, Scott HS, Rossier C, Seeburg PH, Higuchi M, Antonarakis SE (1997) Cloning of a human RNA editing deaminase (ADARB1) of glutamate receptors that maps to chromosome 21q22.3. Genomics 41:210-17 CrossRef
  24. Nishikura K (2010) Functions and regulation of RNA editing by ADAR2 deaminases. Annu Rev Biochem 79:321-49 CrossRef
  25. Park MW, Kim CH, Cheong JH, Bak KH, Kim JM, Oh SJ (2006) Occludin expression in brain tumors and its relevance to peritumoral edema and survival. Cancer Res Treat 38:139-43 CrossRef
  26. Paz N, Levanon EY, Amariglio N, Heimberger AB, Ram Z, Constantini S, Barbash ZS, Adamsky K, Safran M, Hirschberg A, Krupsky M, Ben-Dov I, Cazacu S, Mikkelsen T, Brodie C, Eisenberg E, Rechavi G (2007) Altered adenosine-to-inosine RNA editing in human cancer. Genome Res 17:1586-595 CrossRef
  27. Rueter SM, Dawson TR, Emeson RB (1999) Regulation of alternative splicing by RNA editing. Nature 399:75-0 CrossRef
  28. Skarda J, Amariglio N, Rechavi G (2009) RNA editing in human cancer: review. APMIS 117:551-57 CrossRef
  29. Slavov D, Gardiner K (2002) Phylogenetic comparison of the pre-mRNA adenosine deaminase ADAR2 genes and transcripts: conservation and diversity in editing site sequence and alternative splicing patterns. Gene 299:83-4 CrossRef
  30. Tamiya T, Ono Y, Matsumoto K, Ohmoto T (2001) Peritumoral brain edema in intracranial meningiomas: effects of radiological and histological factors. Neurosurgery 49:1046-051
  31. Tariq A, Jantsch MF (2012) Transcript diversification in the nervous system: A to I RNA editing in CNS function and disease development. Front Neurosci 6:99 CrossRef
  32. Tomaselli S, Galeano F, Massimi L, Rocco CD, Lauriola L, Mastronuzzi A, Locatelli F, Gallo A (2013) ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grade astrocytomas. BMC Cancer 13:255 CrossRef
  33. Wang P, Ni RY, Chen MN, Mou KJ, Mao Q, Liu YH (2011) Expression of aquaporin-4 in human supratentorial meningiomas with peritumoral brain edema and correlation of VEGF with edema formation. Genet Mol Res 10:2165-171 CrossRef
  34. Wright A, Vissel B (2012) The essential role of AMPA receptor GluA2 subunit RNA editing in the normal and diseased brain. Front Mol Neurosci 5:34
  
• 作者单位：Jun Wei (1)
  Zhaohui Li (1)
  Chao Du (1)
  Bin Qi (2)
  Xingli Zhao (1)
  Liping Wang (3)
  Lirong Bi (4)
  Guan Wang (1)
  Xuan Zhang (5)
  Xiaoyun Su (6)
  Yuzhuo Pan (7)
  Yu Tian (1)
  
  1. Department of Neurosurgery, China–Japan Union Hospital, Jilin University, Changchun, 130033, China
  2. Department of Neurosurgery, the First Hospital of Jilin University, Changchun, 130021, China
  3. Department of Pathology, China–Japan Union Hospital, Jilin University, Changchun, 130033, China
  4. Department of Pathology, the First Hospital of Jilin University, Changchun, 130033, China
  5. Department of Science and Education, the Second Hospital of Jilin University, 130012, Changchun, China
  6. College of Pharmacy, Jilin University, Changchun, 130021, China
  7. Department of Pharmaceutical Science, School of Pharmacy and Pharmaceutical Science, State University of New York Buffalo, 559 Cooke Hall, Buffalo, NY, 14260, USA
  
• ISSN：0942-0940

文摘

Background RNA editing is catalyzed by adenosine deaminases acting on RNA (ADARs). ADAR2 is the main enzyme responsible for recoding editing in humans. Adenosine-to-inosine (A-to-I) editing at the Q/R site is reported to be decreased in gliomas; however, the expression of ADAR2 mRNA was not greatly affected. Methods We determined ADAR2 mRNA expression in human glioblastoma cell lines and in normal human glial cells by real-time RT-PCR. We also determined ADAR2 mRNA expression in 44 glioma tissues and normal white matter. After identifying an alternative splicing variant (ASV) of ADAR2 in gliomas, we performed sequencing. We then classified glioblastomas based on the presence (+) or absence (- of the ASV to determine the correlations between ASV-?and malignant features of glioblastomas, such as invasion, peritumoral brain edema, and survival time. Results There were no significant differences in ADAR2 mRNA expression among human glioblastoma cell lines or in gliomas compared with normal white matter (all p-gt;-.05). The ASV, which contained a 47-nucleotide insertion in the ADAR2 mRNA transcript, was detected in the U251 and BT325 cell lines, and in some glioma tissues. The expression rate of ASV differed among gliomas of different grades. ASV-?glioblastomas were more malignant than ASV -glioblastomas. Conclusions ADAR2 is a family of enzymes in which ASVs result in differences in enzymatic activity. The ADAR2 ASV may be correlated with the invasiveness of gliomas. Identification of the mechanistic characterization of ADAR2 ASV may have future potential for individualized molecular targeted-therapy for glioma.