Downregulation of miR-34a in breast tumors is not associated with either p53 mutations or promoter hypermethylation while it correlates with metastasis

MicroRNA-34 family has anti-proliferative and apoptotic roles. Recent studies have shown that p53 upregulates miR-34 family leading to direct repression of several key oncogenes. Inactivation of miR-34a has been reported in multiple types of malignancies including breast cancer. The critical role of miR-34a in p53-mediated cell cycle arrest and apoptosis invokes studies focusing on the specific role of miR-34a dysregulation in carcinogenesis. While presence of p53 mutations has frequently been described in breast cancer, still most of the breast tumors do not show any variation in the p53 coding sequence or protein expression. Therefore, it is important to clarify possible involvement of other mediators of p53 pathway in breast cancer. In this study, expression of mature miR-34a in breast tumors with wild-type p53 was investigated in order to find any correlation between dysregulation of miR-34a expression and breast cancer. In about 40 % of the wild-type p53 samples, miR-34a was significantly downregulated. Neither hypermethylation of the miR-34a promoter nor genetic variations of the p53-binding site were detected in tumor samples with downregulated miR-34a. This study has provided evidence that miR-34a expression can be affected in a significant proportion of breast tumors independent of p53. Furthermore, downregulation of miR-34a was significantly associated with metastasis, while there was a significant correlation between upregulation of miR-34a and non-metastatic condition indicating a protective role for miR-34a against more invasive disease. Knowledge of miR-34a status may provide additional useful information regarding the nature of breast tumors, especially when p53 testing does not show any aberration.