Interrelation of the Circulating and Tissue MicroRNA-21 with Tissue PDCD4 Expression and the Invasiveness of Iraqi Female Breast Tumors.

Abstract

The changes in the translational repression and variation in mRNA degradation induced by micro RNA are important aspects of tumorigenesis. The association of microRNA-21 with clinicopathologic features and expression of programed cell death 4 (PDCD4) in Iraqi female's with breast tumors has not been studied. MicroRNAs were extracted from a set of 60 breast tumor tissues and blood samples of females with breast cancer and benign breast lesions obtained after breast-reductive surgery, and only blood samples from 30 normal volunteers. These extracts were evaluated for miR-21 expression by quantitative RT-PCR. Analysis of PDCD4 protein expression was carried out as miR-21 target gene by immunohistochemical tests and correlating the results with patients' clinicopathological features. Significant overexpression of miRNA-21 was found in breast cancer group. The fold increase in the miR-21 gene expression was significantly higher in circulating exosomes and breast tissues of breast cancer patients as compared to other groups (P<0.001). Overexpression of miR-21 was also significantly associated with the advanced tumor stage and histological grade. In breast cancer patients, PDCD4 protein expression was decreased to about 70% of the level in the control group. The delta Ct of exosomal and breast tissue miRNA-21 was negatively associated with PDCD4 expression. In conclusion, the translational repression of the PDCD4 induced by the high expression of miR-21 promotes breast cell transformation and development of breast tumor, and circulating miR-21 level could be applied to the screening panels for early detection of women breast cancer.