ADAR2-Mediated Editing of miR-214 and miR-122 Precursor and Antisense RNA Transcripts in Liver Cancers

A growing list of microRNAs (miRNAs) show aberrant expression patterns in hepatocellular carcinoma (HCC), but the regulatory mechanisms largely remain unclear. RNA editing catalyzed by members of the adenosine deaminase acting on the RNA (ADAR) family could target the miRNA precursors and affect the...

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Main Authors: Liu, Wan-Hsin, Chen, Chao-Hung, Yeh, Kun-Huei, Li, Chiao-Ling, Wu, Yi-Jinn, Chen, Ding-Shinn, Chen, Pei-Jer, Yeh, Shiou-Hwei
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873926/
id pubmed-3873926
recordtype oai_dc
spelling pubmed-38739262014-01-02 ADAR2-Mediated Editing of miR-214 and miR-122 Precursor and Antisense RNA Transcripts in Liver Cancers Liu, Wan-Hsin Chen, Chao-Hung Yeh, Kun-Huei Li, Chiao-Ling Wu, Yi-Jinn Chen, Ding-Shinn Chen, Pei-Jer Yeh, Shiou-Hwei Research Article A growing list of microRNAs (miRNAs) show aberrant expression patterns in hepatocellular carcinoma (HCC), but the regulatory mechanisms largely remain unclear. RNA editing catalyzed by members of the adenosine deaminase acting on the RNA (ADAR) family could target the miRNA precursors and affect the biogenesis process. Therefore, we investigate whether RNA editing could be one mechanism contributing to the deregulation of specific miRNAs in HCC. By overexpression of individual ADARs in hepatoma cells, RNA editing on the precursors of 16 miRNAs frequently deregulated in HCC was screened by a sensitive high-resolution melting platform. The results identified RNA precursors of miR-214 and miR-122 as potential targets edited by ADAR2. A subset of HCC showing elevated ADAR2 verified the major editings identified in ARAR2 overexpressed hepatoma cells, either with A-to-I or U-to-C changes. The unusual U-to-C editing at specific residues was demonstrated as being attributed to the A-to-I editing on the RNA transcripts complementary to the pri-miRNAs. The editing event caused a decrease of the RNA transcript complementary to pri-miR-214, which led to the decrease of pri-miR-214 and miR-214 and resulted in the increased protein level of its novel target gene Rab15. In conclusion, the current study discovered ADAR2-mediated editing of the complementary antisense transcripts as a novel mechanism for regulating the biogenesis of specific miRNAs during hepatocarcinogenesis. Public Library of Science 2013-12-27 /pmc/articles/PMC3873926/ /pubmed/24386085 http://dx.doi.org/10.1371/journal.pone.0081922 Text en © 2013 Liu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Liu, Wan-Hsin
Chen, Chao-Hung
Yeh, Kun-Huei
Li, Chiao-Ling
Wu, Yi-Jinn
Chen, Ding-Shinn
Chen, Pei-Jer
Yeh, Shiou-Hwei
spellingShingle Liu, Wan-Hsin
Chen, Chao-Hung
Yeh, Kun-Huei
Li, Chiao-Ling
Wu, Yi-Jinn
Chen, Ding-Shinn
Chen, Pei-Jer
Yeh, Shiou-Hwei
ADAR2-Mediated Editing of miR-214 and miR-122 Precursor and Antisense RNA Transcripts in Liver Cancers
author_facet Liu, Wan-Hsin
Chen, Chao-Hung
Yeh, Kun-Huei
Li, Chiao-Ling
Wu, Yi-Jinn
Chen, Ding-Shinn
Chen, Pei-Jer
Yeh, Shiou-Hwei
author_sort Liu, Wan-Hsin
title ADAR2-Mediated Editing of miR-214 and miR-122 Precursor and Antisense RNA Transcripts in Liver Cancers
title_short ADAR2-Mediated Editing of miR-214 and miR-122 Precursor and Antisense RNA Transcripts in Liver Cancers
title_full ADAR2-Mediated Editing of miR-214 and miR-122 Precursor and Antisense RNA Transcripts in Liver Cancers
title_fullStr ADAR2-Mediated Editing of miR-214 and miR-122 Precursor and Antisense RNA Transcripts in Liver Cancers
title_full_unstemmed ADAR2-Mediated Editing of miR-214 and miR-122 Precursor and Antisense RNA Transcripts in Liver Cancers
title_sort adar2-mediated editing of mir-214 and mir-122 precursor and antisense rna transcripts in liver cancers
description A growing list of microRNAs (miRNAs) show aberrant expression patterns in hepatocellular carcinoma (HCC), but the regulatory mechanisms largely remain unclear. RNA editing catalyzed by members of the adenosine deaminase acting on the RNA (ADAR) family could target the miRNA precursors and affect the biogenesis process. Therefore, we investigate whether RNA editing could be one mechanism contributing to the deregulation of specific miRNAs in HCC. By overexpression of individual ADARs in hepatoma cells, RNA editing on the precursors of 16 miRNAs frequently deregulated in HCC was screened by a sensitive high-resolution melting platform. The results identified RNA precursors of miR-214 and miR-122 as potential targets edited by ADAR2. A subset of HCC showing elevated ADAR2 verified the major editings identified in ARAR2 overexpressed hepatoma cells, either with A-to-I or U-to-C changes. The unusual U-to-C editing at specific residues was demonstrated as being attributed to the A-to-I editing on the RNA transcripts complementary to the pri-miRNAs. The editing event caused a decrease of the RNA transcript complementary to pri-miR-214, which led to the decrease of pri-miR-214 and miR-214 and resulted in the increased protein level of its novel target gene Rab15. In conclusion, the current study discovered ADAR2-mediated editing of the complementary antisense transcripts as a novel mechanism for regulating the biogenesis of specific miRNAs during hepatocarcinogenesis.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873926/
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