共 55 条
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
被引:35
作者:
Liu, Linhua
[1
]
Jiang, Yiguo
[1
]
Zhang, Hongyu
[2
]
Greenlee, Anne R.
[3
]
Yu, Rian
[4
]
Yang, Qiaoyuan
[1
]
机构:
[1] Guangzhou Med Univ, Inst Chem Carcinogenesis, State Key Lab Resp Dis, Guangzhou 510182, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Dept Med Oncol, Affiliated Hosp 5, Zhuhai 519000, Peoples R China
[3] Jackson Lab, Stem Cell & Primary Cell Facil, Bar Harbor, ME 04609 USA
[4] Guangdong Pharmaceut Univ, Dept Occupat & Environm Hlth, Sch Publ Hlth, Guangzhou 510310, Guangdong, Peoples R China
基金:
中国国家自然科学基金;
关键词:
Anti-BPDE;
Malignant transformation;
MicroRNA;
miR-22;
PTEN;
LUNG-CANCER;
PHOSPHORYLATED AKT;
MIRNA EXPRESSION;
PTEN EXPRESSION;
TUMOR-GROWTH;
GENE;
CARCINOMA;
MICRORNA-21;
INVASION;
BREAST;
D O I:
10.1016/j.tiv.2010.02.016
中图分类号:
R99 [毒物学(毒理学)];
学科分类号:
100405 ;
摘要:
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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页码:1168 / 1175
页数:8
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