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.

Clinical Translatability of “Identified” Circulating miRNAs for Diagnosing Breast Cancer: Overview and Update

“…An in-depth analysis of the data suggested that circulating miRNAs were identified as potential diagnostic biomarkers for BC lacked specificity and often showed discordant expression in the blood and tissue of patients affected with cancer. The final processing of our in-depth analysis revealed that a circulating miRNA signature for BC diagnosis is currently unavailable because the most frequently studied circulating miRNA, BC-associated miRNAs (miR-155, miR-21, miR-195, and miR-145), except for miR-195, are the most non-specific BC-associated miRNAs, although some of these miRNAs were able to discriminate patients with BC from patients with benign breast lesions (BBLs) (miR-21 [69,78]; miR-155 [79,80]; miR-145 and miR-195 [61]). Factors triggering neoplastic transformation may differ among tumors, but the common denominator for all neoplastic diseases is uncontrolled cell growth and the activation of inflammatory processes.…”

“…Among all miRNAs included in Table 2, miR-21 was the most commonly validated and proposed as a potential diagnostic biomarker for BC either alone [69] or in combination with other circulating miRNAs [43,56,61,64,70]. Regardless of the biological sample (plasma or serum), miR-21 was always upregulated both in the bloodstream and tissue.…”

Recent Discoveries of Macromolecule- and Cell-Based Biomarkers and Therapeutic Implications in Breast Cancer

“…As mentioned earlier, miR-21 is overexpressed in breast cancer ( Section 4.2 , [ 46 ]). miR-21 promotes the transformation and development of breast cancer by inhibiting the expression of programmed cell death protein 4 [ 49 ]. MiR-182, a member of the miR-183 family, is packed into exosomes.…”

The Emerging Role of MicroRNAs in Breast Cancer

“…miR-10b is highly expressed in early metastatic and recurrent BC patients [20] and is associated with increased proliferation, migration, and invasion of BC cells via E-cadherin targeting [21]. miR-21 was demonstrated to promote the transformation and development of BC via suppressing the programmed cell death protein 4 (PDCD4) expression [22]. miR-155 acts as an onco-miRNA in BC, which inhibition by an antisense oligonucleotide remarkably prevented proliferation and induced cell apoptosis [23,24].…”