Downregulation of miR-143/145 Cluster in Breast Carcinoma Specimens: Putative Role of DNA Oncoviruses

Abstract

Background: The DNA oncoviruses, including human papillomavirus (HPV) and Epstein-Barr virus (EBV) are among the most important infectious agents involved in breast carcinogenesis. These oncoviruses have a broad disrupting effect on cellular miRNAs and their functions, by which they contribute to carcinogenesis. Objectives: In this investigation, we evaluated the correlation between HPV and EBV and the expression level of tumor suppressor miRNAs (miR-143 and 145), clinical outcomes, and their association with stimulating inflammatory cytokines in patients with breast carcinoma. Methods: In our case-control study, 35 cancerous tissues and 35 adjacent non-cancerous tissues were collected from 35 patients. Nested-PCR was set up for the detection of HPV and EBV genomes, and RT-qPCR was used for miRNA expression in the case and control groups. In addition, serum specimens were obtained from all patients (n = 35) and healthy controls (n = 35) to determine the IL-8 serum concentration. Results: We found HPV and EBV in 14.2% (10/70) and 7% (5/70) of all samples, respectively. The distributions of positive samples in the case and control groups were 25.7% (9/35) and 2.9% (1/35) (P = 0.006) for HPV and 11.4% (4/35) and 2.9% (1/35) (P = 0.164) for EBV, respectively. Besides, RT-qPCR showed that miR-143 and miR-145 were significantly downregulated in HPV and EBV-infected cases compared to non-infected ones (P < 0.05). Data also indicated that the promotion of metastasis status was related to miR-143/145 downregulation and HPV infection (P = 0.003). No significant difference was found in serum IL-8 concentration concerning viral infections. Conclusions: Our results suggested the possible involvement of viral infections in breast carcinogenesis and adverse clinical outcomes by downregulating miR-143/145.