Altered adenosine-to-inosine RNA editing in human cancer

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. Exper...

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Bibliographic Details
Published in:Genome Research 2007-11, Vol.17 (11), p.1586-1595
Main Authors: Paz, Nurit, Levanon, Erez Y, Amariglio, Ninette, Heimberger, Amy B, Ram, Zvi, Constantini, Shlomi, Barbash, Zohar S, Adamsky, Konstantin, Safran, Michal, Hirschberg, Avi, Krupsky, Meir, Ben-Dov, Issachar, Cazacu, Simona, Mikkelsen, Tom, Brodie, Chaya, Eisenberg, Eli, Rechavi, Gideon
Format: Article
Language:English
Subjects:
Adenosine - chemistry
Adenosine Deaminase - genetics
Alu Elements
Animals
Base Sequence
Cell Line, Tumor
Cell Proliferation
Cells, Cultured
Computational Biology
Humans
Inosine - chemistry
Letter
Mice
Molecular Sequence Data
Neoplasms - genetics
Neoplasms - metabolism
RNA Editing
RNA Precursors
RNA, Untranslated - metabolism
RNA-Binding Proteins
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Summary: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.
ISSN:1088-9051
1549-5469
1549-5477
DOI:10.1101/gr.6493107