Document Detail


miR-22 functions as a micro-oncogene in transformed human bronchial epithelial cells induced by anti-benzo[a]pyrene-7,8-diol-9,10-epoxide.
MedLine Citation:
PMID:  20170724     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively control the expression of target genes post-transcriptionally. In this study, transformed human bronchial epithelial cells induced by anti-benzo[a]pyrene-7,8-diol-9,10-epoxide were characterized for miRNA involved in carcinogenesis. We found miR-22, which was highly expressed in transformed cells, concomitant with downregulation of the tumour suppressor gene PTEN protein. Using computer-generated and experimental analysis, PTEN was identified as one of the targets of miR-22. Over-expression and inhibition studies of miRNA showed decreased and increased PTEN protein, respectively, with no alteration of PTEN mRNA levels. These findings suggest that miR-22 regulates PTEN expression through translational repression. A dual-reporter assay confirmed these findings and provided evidence to suggest that miR-22 regulates PTEN expression by binding with a target site in the PTEN 3'-untranslated region. A mutated seed sequence in the PTEN binding site can abrogate the regulatory role of miR-22 on PTEN. Moreover, we found that anti-miR-22 promoted cell apoptosis, decreased colony formation and reduced the motility of malignant cells. Together, the results indicate that miR-22 functions as a micro-oncogene that can invert the functionality of PTEN. Furthermore, the binding site for miR-22 might provide insight into a potential target for gene therapy.
Authors:
Linhua Liu; Yiguo Jiang; Hongyu Zhang; Anne R Greenlee; Rian Yu; Qiaoyuan Yang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-17
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  24     ISSN:  1879-3177     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-17     Completed Date:  2010-06-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  1168-75     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182, PR China.
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MeSH Terms
Descriptor/Qualifier:
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / toxicity*
Bronchi / cytology
Carcinogens / toxicity*
Cell Line, Transformed
Humans
MicroRNAs / metabolism*
Oncogenes
PTEN Phosphohydrolase / genetics*,  metabolism
Respiratory Mucosa / drug effects*,  metabolism
Chemical
Reg. No./Substance:
0/Carcinogens; 0/MIRN22 microRNA, human; 0/MicroRNAs; 55097-80-8/7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; EC 3.1.3.67/PTEN Phosphohydrolase

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