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.
引用
收藏
页码:1168 / 1175
页数:8
相关论文
共 55 条
[1]   microRNAs: Tiny regulators with great potential [J].
Ambros, V .
CELL, 2001, 107 (07) :823-826
[2]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[3]   Phylogenetic shadowing and computational identification of human microRNA genes [J].
Berezikov, E ;
Guryev, V ;
van de Belt, J ;
Wienholds, E ;
Plasterk, RHA ;
Cuppen, E .
CELL, 2005, 120 (01) :21-24
[4]   bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila [J].
Brennecke, J ;
Hipfner, DR ;
Stark, A ;
Russell, RB ;
Cohen, SM .
CELL, 2003, 113 (01) :25-36
[5]   Benzo[a] pyrene-7,8-dihydrodiol promotes checkpoint activation and G2/M arrest in human bronchoalveolar carcinoma H358 cells [J].
Caino, M. Cecilia ;
Oliva, Jose L. ;
Jiang, Hao ;
Penning, Trevor M. ;
Kazanietz, Marcelo G. .
MOLECULAR PHARMACOLOGY, 2007, 71 (03) :744-750
[6]   MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells [J].
Chan, JA ;
Krichevsky, AM ;
Kosik, KS .
CANCER RESEARCH, 2005, 65 (14) :6029-6033
[7]   MicroRNAs as oncogenes and tumor suppressors [J].
Chen, CZ .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (17) :1768-1771
[8]   Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis [J].
Cheng, AM ;
Byrom, MW ;
Shelton, J ;
Ford, LP .
NUCLEIC ACIDS RESEARCH, 2005, 33 (04) :1290-1297
[9]   MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines [J].
Crawford, M. ;
Brawner, E. ;
Batte, K. ;
Yu, L. ;
Hunter, M. G. ;
Otterson, G. A. ;
Nuovo, G. ;
Marsh, C. B. ;
Nana-Sinkam, S. P. .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 373 (04) :607-612
[10]   MORTALITY IN RELATION TO SMOKING - 20 YEARS OBSERVATIONS ON MALE BRITISH DOCTORS [J].
DOLL, R ;
PETO, R .
BRITISH MEDICAL JOURNAL, 1976, 2 (6051) :1525-1536