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

Abstract 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-α, HIF-α, VEGF, CD31 and Ki67 in tumor tissue. The combination tamoxifen and/or letrozole with the exercise training could down-regulate the expression of ERα, miR-21, HIF-1α, TNF-α, 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.