期刊
TOXICOLOGY IN VITRO
卷 24, 期 4, 页码 1168-1175出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2010.02.016
关键词
Anti-BPDE; Malignant transformation; MicroRNA; miR-22; PTEN
类别
资金
- National Natural Science Foundation of China [30571546, 30771780]
- Scientific Research Foundation of the State Education Ministry for Returned Overseas Chinese Scholars [2007-24]
- Natural Science Foundation of Guangdong Province [07117550, 9251018201000004]
- Higher Education Institutions of Guangdong Province, China [06Z021]
- Science and Technology Program of Guangzhou Bureau of Education, China [08A093, 08A092]
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. (C) 2010 Elsevier Ltd. All rights reserved.
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