MiRNA-218 Is Frequently Downregulated in Malignant Breast Tumors: A Footprint of Epstein-Barr Virus Infection

Background Objective: The role of Epstein-Barr Virus in development of breast cancer is frequently studied. In this regard, miRNAs are among the contributing elements in the molecular pathophysiology of EBV-related diseases. In addition, a growing number of host miRNAs are believed to be implicated in pathogenesis of breast cancer. MiR-218 is a tumor suppressive miRNA that is subjected to dysregulation in various EBV-associated cancers. We aimed to investigate the frequency of EBV and its relationship with expression status of tumor suppressive miR-218 in breast cancer and adjacent normal tissue. Methods: A total number of 51 fresh malignant breast cancer tissues (cases) and their adjacent normal tissues (controls) were collected. Nested-PCR and RT-qPCR were set to identify EBV frequency and miR-218 expression in cases and controls, respectively. Results: Out of all samples, 6.8% (7/102) comprising 11.6% (6/51) in malignant tissues and 1.9% (1/51) in normal control tissues were positive for EBV (P 0.05). Quantitative data showed that miR-218 was significantly downregulated in malignant tissues compared to control tissues (P 0.0001). In addition, reduced expression of miR-218 was associated with adverse clinical outcomes, metastasis, and higher grades of malignancy. Given the presence of EBV, lower expression of miR-218 was observed in breast cancer group in comparison with normal group (P 0.05). Conclusion: Our results raise the possibility of the relation between EBV infection and miR-218 downregulation in breast cancer and propose further investigations in this regard.