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

Life Sci. 2016 Apr 15:151:30-40. doi: 10.1016/j.lfs.2016.02.090. Epub 2016 Feb 26.

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.

Keywords: Exercise training; Letrozole; Tamoxifen; breast cancer; let-7; miR-206; miR-21.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / therapy
  • Animals
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism
  • Combined Modality Therapy
  • Exercise Therapy / methods*
  • Female
  • Letrozole
  • Mammary Neoplasms, Experimental / genetics*
  • Mammary Neoplasms, Experimental / therapy
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Muscle, Skeletal / metabolism
  • Neovascularization, Pathologic / prevention & control*
  • Nitriles / administration & dosage
  • Signal Transduction* / drug effects
  • Tamoxifen / administration & dosage
  • Triazoles / administration & dosage

Substances

  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • MIRN-21 microRNA, mouse
  • MicroRNAs
  • Mirn206 microRNA, mouse
  • Nitriles
  • Triazoles
  • mirnlet7 microRNA, mouse
  • Tamoxifen
  • Letrozole