MicroRNA-206, let-7a and microRNA-21 pathways involved in the anti-angiogenesis effects of the interval exercise training and hormone therapy in breast cancer

Aims: MicroRNAs (miRNAs) are the targeting signal-transduction pathways that can mediate tumorigenesis via their down and/or up-regulation. For example, miR-21 and miR-206 can effect on the tumor angiogenesis as an oncomir and a tumor suppressor, respectively. Materials and methods: The present study is aimed to investigate the effects of the interval exercise training in combination with tamoxifen and/or letrozole on miR-21, miR-206 and let-7 as well as their underlying pathways in regard to tumor angiogenesis in sixty four mice with breast tumor. ELISA, immunohistochemistry, qRT-PCR assays were performed accomplish the study. Key findings: The results showed that the tumor size was significantly declined in the exercise training, tamoxifen and letrozole groups compared to tumor group. Mir-206 and let-7 were up-regulated, and mir-21 expression was down-regulated in the exercise training compared to tumor group. Exercise training decreased the expression of ER-alpha, HIF-alpha, VEGF, CD31 and Ki67 in tumor tissue. The combination tamoxifen and/or letrozole with the exercise training could down-regulate the expression of ER alpha, miR-21, HIF-1 alpha, TNF-alpha, CD31, Ki67 and VEGF, and up-regulate the expression of miR-206, PDCD-4, let-7 and IL-10 that led to reducing the angiogenesis and tumor growth. Significance: Our results showed that miR-21, miR-206 and let-7a pathways may involve in the anti-angiogenesis effects of the interval exercise training with hormone therapy in mice model of breast tumor. (C) 2016 Elsevier Inc. All rights reserved.