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Chandra, S., Khatoon, R., Pandey, A., Saini, S., Vimal, D., Singh, P., Chowdhuri, D.K. (2016). dme-miR-314-3p modulation in Cr(VI) exposed Drosophila affects DNA damage repair by targeting mus309.  J. Hazard. Mater. 304(): 360--369.
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microRNAs (miRNAs) as one of the major epigenetic modulators negatively regulate mRNAs at post transcriptional level. It was therefore hypothesized that modulation of miRNAs by hexavalent Chromium Cr(VI), a priority environmental chemical, can affect DNA damage. In a genetically tractable model, Drosophila melanogaster, role of maximally up-regulated miRNA, dme-miR-314-3p, on DNA damage was examined by exposing the third instar larvae to 5.0-20.0μg/ml Cr(VI) for 24 and 48h. mus309, a Drosophila homologue of human Bloom's syndrome and predicted as one of the potential targets of this miRNA, was confirmed as its target by 5'RLM-RACE assay. A significant down-regulation of mus309 was observed in dme-miR-314-3p overexpression strain (myo-gal4>UAS-miR-314-3p) as compared with that in parental strains (myo-gal4 and UAS-miR-314-3p) and in w(1118). A significant increase in DNA damage including double strand breaks generation was observed in exposed myo-gal4>UAS-miR-314 and mus309 mutants as compared with that in parental strain and in unexposed control. A significant down-regulation of cell cycle regulation genes (CycA, CycB and cdc2) was observed in these exposed genotypes. Collectively, the study demonstrates that dme-miR-314-3p can mediate the downregulation of repair deficient gene mus309 leading to increased DNA damage and cell cycle arrest in exposed organism which may affect Cr(VI) mediated carcinogenesis.

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    J. Hazard. Mater.
    Journal of hazardous materials
    0304-3894 1873-3336
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