title: 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.
abstract: 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.affiliation: Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182, PR China.
authors.forename: Linhua
authors.initials: L
authors.lastname: Liu
authors.forename: Yiguo
authors.initials: Y
authors.lastname: Jiang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Anne R
authors.initials: AR
authors.lastname: Greenlee
authors.forename: Rian
authors.initials: R
authors.lastname: Yu
authors.forename: Qiaoyuan
authors.initials: Q
authors.lastname: Yang
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology; D002273:Carcinogens / Q000633:toxicity*; D002461:Cell Line, Transformed; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009857:Oncogenes; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002273:Carcinogens; C548375:MIRN22 microRNA, human; D035683:MicroRNAs; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D051059:PTEN Phosphohydrolase