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.

The diagnostic significance of circulating miRNAs and metabolite profiling in early prediction of breast cancer in Egyptian women

“…Our finding was also comparable with the study by Ibrahim et al 2020, which reported that the plasma expression level of miRNA-145 (AUC = 0.70) was recorded to be significantly decreased ( P < 0.01) at the initial BC diagnosis, as compared to healthy individuals. Also, Iorioet al ( 2005 ) identified miRNA-145 to be down-regulated in breast cancer tissues as compared to normal tissues (Nakhaie et al 2020 ; Tsai et al 2018 ; Quan et al 2018 ). This detected reduction in the expression level of miRNA-145 in BC cases was suggested to be as a result of the methylation of its promoter (Liu et al 2017 ).…”