Post-transcriptional regulation of Rad51c by miR-222 contributes cellular transformation.

Post-transcriptional regulation of Rad51c by miR-222 contributes cellular transformation.

Blog Article

DNA repair inhibition has been described as an essential event leading to the initiation of carcinogenesis.In a previous study, we observed that the exposure to metal mixture induces changes in the miR-nome of the cells that was correlated with the sub-expression of mRNA involved in processes and diseases associated with metal exposure.From this analysis, size-matters-enlargers one of the miRNAs that shows changes in its expression is miR-222, which is overexpressed in various cancers associated with exposure to metals.In silico studies showed that a possible target for the microRNA-222 could be Rad 51c, a gene involved in the double-stranded DNA repair.

We could appreciate that up-regulation of miR-222 reduces the expression both gene and as a protein expression of Rad51c by RT-PCR and immunoblot, respectively.A luciferase assay was performed to validate Rad51c as miR-222 target.Neutral comet assay was performed in order to evaluate Lip Treatment DNA double-strand breaks under experimental conditions.Here, we demonstrate that miR-222 up-regulation, directly regulates Rad51c expression negatively, and impairs homologous recombination of double-strand break DNA repair during the initiation stage of cell transformation.

This inhibition triggers morphological transformation in a two-stage Balb/c 3T3 cell assay, suggesting that this small RNA acts as an initiator of the carcinogenesis process.