RT Journal
A1 Paz, Nurit
A1 Levanon, Erez Y.
A1 Amariglio, Ninette
A1 Heimberger, Amy B.
A1 Ram, Zvi
A1 Constantini, Shlomi
A1 Barbash, Zohar S.
A1 Adamsky, Konstantin
A1 Safran, Michal
A1 Hirschberg, Avi
A1 Krupsky, Meir
A1 Ben-Dov, Issachar
A1 Cazacu, Simona
A1 Mikkelsen, Tom
A1 Brodie, Chaya
A1 Eisenberg, Eli
A1 Rechavi, Gideon
T1 Altered adenosine-to-inosine RNA editing in human cancer
JF Genome Research 
JO Genome Research 
YR 2007 
FD November 01 
VO 17 
IS 11 
SP 1586 
OP 1595 
DO 10.1101/gr.6493107 
UL http://genome.cshlp.org/content/17/11/1586.abstract 
AB Adenosine-to-inosine (A-to-I) RNA editing was recently shown to be abundant in the human transcriptome, affecting thousands of genes. Employing a bioinformatic approach, we identified significant global hypoediting of Alu repetitive elements in brain, prostate, lung, kidney, and testis tumors. Experimental validation confirmed this finding, showing significantly reduced editing in Alu sequences within MED13 transcripts in brain tissues. Looking at editing of specific recoding and noncoding sites, including in cancer-related genes, a more complex picture emerged, with a gene-specific editing pattern in tumors vs. normal tissues. Additionally, we found reduced RNA levels of all three editing mediating enzymes, ADAR, ADARB1, and ADARB2, in brain tumors. The reduction of ADARB2 correlated with the grade of malignancy of glioblastoma multiforme, the most aggressive of brain tumors, displaying a 99% decrease in ADARB2 RNA levels. Consistently, overexpression of ADAR and ADARB1 in the U87 glioblastoma multiforme cell line resulted in decreased proliferation rate, suggesting that reduced A-to-I editing in brain tumors is involved in the pathogenesis of cancer. Altered epigenetic control was recently shown to play a central role in oncogenesis. We suggest that A-to-I RNA editing may serve as an additional epigenetic mechanism relevant to cancer development and progression.