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Tumor suppressor miR-375 regulates MYC expression via repression of CIP2A coding sequence through multiple miRNA–mRNA interactions

MicroRNAs (miRNAs) are small, noncoding RNAs involved in posttranscriptional regulation of protein-coding genes in various biological processes. In our preliminary miRNA microarray analysis, miR-375 was identified as the most underexpressed in human oral tumor versus controls. The purpose of the pre...

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Autores principales: Jung, Hyun Min, Patel, Rushi S., Phillips, Brittany L., Wang, Hai, Cohen, Donald M., Reinhold, William C., Chang, Lung-Ji, Yang, Li-Jun, Chan, Edward K. L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667718/
https://www.ncbi.nlm.nih.gov/pubmed/23552692
http://dx.doi.org/10.1091/mbc.E12-12-0891
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author Jung, Hyun Min
Patel, Rushi S.
Phillips, Brittany L.
Wang, Hai
Cohen, Donald M.
Reinhold, William C.
Chang, Lung-Ji
Yang, Li-Jun
Chan, Edward K. L.
author_facet Jung, Hyun Min
Patel, Rushi S.
Phillips, Brittany L.
Wang, Hai
Cohen, Donald M.
Reinhold, William C.
Chang, Lung-Ji
Yang, Li-Jun
Chan, Edward K. L.
author_sort Jung, Hyun Min
collection PubMed
description MicroRNAs (miRNAs) are small, noncoding RNAs involved in posttranscriptional regulation of protein-coding genes in various biological processes. In our preliminary miRNA microarray analysis, miR-375 was identified as the most underexpressed in human oral tumor versus controls. The purpose of the present study is to examine the function of miR-375 as a candidate tumor suppressor miRNA in oral cancer. Cancerous inhibitor of PP2A (CIP2A), a guardian of oncoprotein MYC, is identified as a candidate miR-375 target based on bioinformatics. Luciferase assay accompanied by target sequence mutagenesis elucidates five functional miR-375–binding sites clustered in the CIP2A coding sequence close to the C-terminal domain. Overexpression of CIP2A is clearly demonstrated in oral cancers, and inverse correlation between miR-375 and CIP2A is observed in the tumors, as well as in NCI-60 cell lines, indicating the potential generalized involvement of the miR-375–CIP2A relationship in many other cancers. Transient transfection of miR-375 in oral cancer cells reduces the expression of CIP2A, resulting in decrease of MYC protein levels and leading to reduced proliferation, colony formation, migration, and invasion. Therefore this study shows that underexpression of tumor suppressor miR-375 could lead to uncontrolled CIP2A expression and extended stability of MYC, which contributes to promoting cancerous phenotypes.
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spelling pubmed-36677182013-08-16 Tumor suppressor miR-375 regulates MYC expression via repression of CIP2A coding sequence through multiple miRNA–mRNA interactions Jung, Hyun Min Patel, Rushi S. Phillips, Brittany L. Wang, Hai Cohen, Donald M. Reinhold, William C. Chang, Lung-Ji Yang, Li-Jun Chan, Edward K. L. Mol Biol Cell Articles MicroRNAs (miRNAs) are small, noncoding RNAs involved in posttranscriptional regulation of protein-coding genes in various biological processes. In our preliminary miRNA microarray analysis, miR-375 was identified as the most underexpressed in human oral tumor versus controls. The purpose of the present study is to examine the function of miR-375 as a candidate tumor suppressor miRNA in oral cancer. Cancerous inhibitor of PP2A (CIP2A), a guardian of oncoprotein MYC, is identified as a candidate miR-375 target based on bioinformatics. Luciferase assay accompanied by target sequence mutagenesis elucidates five functional miR-375–binding sites clustered in the CIP2A coding sequence close to the C-terminal domain. Overexpression of CIP2A is clearly demonstrated in oral cancers, and inverse correlation between miR-375 and CIP2A is observed in the tumors, as well as in NCI-60 cell lines, indicating the potential generalized involvement of the miR-375–CIP2A relationship in many other cancers. Transient transfection of miR-375 in oral cancer cells reduces the expression of CIP2A, resulting in decrease of MYC protein levels and leading to reduced proliferation, colony formation, migration, and invasion. Therefore this study shows that underexpression of tumor suppressor miR-375 could lead to uncontrolled CIP2A expression and extended stability of MYC, which contributes to promoting cancerous phenotypes. The American Society for Cell Biology 2013-06-01 /pmc/articles/PMC3667718/ /pubmed/23552692 http://dx.doi.org/10.1091/mbc.E12-12-0891 Text en © 2013 Jung et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Jung, Hyun Min
Patel, Rushi S.
Phillips, Brittany L.
Wang, Hai
Cohen, Donald M.
Reinhold, William C.
Chang, Lung-Ji
Yang, Li-Jun
Chan, Edward K. L.
Tumor suppressor miR-375 regulates MYC expression via repression of CIP2A coding sequence through multiple miRNA–mRNA interactions
title Tumor suppressor miR-375 regulates MYC expression via repression of CIP2A coding sequence through multiple miRNA–mRNA interactions
title_full Tumor suppressor miR-375 regulates MYC expression via repression of CIP2A coding sequence through multiple miRNA–mRNA interactions
title_fullStr Tumor suppressor miR-375 regulates MYC expression via repression of CIP2A coding sequence through multiple miRNA–mRNA interactions
title_full_unstemmed Tumor suppressor miR-375 regulates MYC expression via repression of CIP2A coding sequence through multiple miRNA–mRNA interactions
title_short Tumor suppressor miR-375 regulates MYC expression via repression of CIP2A coding sequence through multiple miRNA–mRNA interactions
title_sort tumor suppressor mir-375 regulates myc expression via repression of cip2a coding sequence through multiple mirna–mrna interactions
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667718/
https://www.ncbi.nlm.nih.gov/pubmed/23552692
http://dx.doi.org/10.1091/mbc.E12-12-0891
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