title: Abnormal expression of an ADAR2 alternative splicing variant in gliomas downregulates adenosine-to-inosine RNA editing.
abstract: 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 > 0.05). 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.
authors: Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, 130033, China.
authors: Jun
authors: J
authors: Wei
authors: Zhaohui
authors: Z
authors: Li
authors: Chao
authors: C
authors: Du
authors: Bin
authors: B
authors: Qi
authors: Xingli
authors: X
authors: Zhao
authors: Liping
authors: L
authors: Wang
authors: Lirong
authors: L
authors: Bi
authors: Guan
authors: G
authors: Wang
authors: Xuan
authors: X
authors: Zhang
authors: Xiaoyun
authors: X
authors: Su
authors: Yuzhuo
authors: Y
authors: Pan
authors: Yu
authors: Y
authors: Tian
mesh_terms: D000241:Adenosine; D000243:Adenosine Deaminase; D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing / Q000235:genetics*; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D045744:Cell Line, Tumor; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D005910:Glioma / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007288:Inosine; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism*; D017393:RNA Editing; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D007288:Inosine; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D000241:Adenosine