title: 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: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Immunoregulation Research Center, Shahed University, Tehran, Iran; Physical Education Department, Shahed University, Tehran, Iran.
authors.forename: Amin
authors.initials: A
authors.lastname: Isanejad
authors.affiliation: Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: aalizadeh@sina.tums.ac.ir.
authors.forename: Ali Mohammad
authors.initials: AM
authors.lastname: Alizadeh
authors.affiliation: Department of Exercise Physiology, Islamic Azad University, Science and Research Branch, Tehran, Iran.
authors.forename: Sadegh
authors.initials: S
authors.lastname: Amani Shalamzari
authors.affiliation: Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Khodayari
authors.affiliation: Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Khodayari
authors.affiliation: Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Khori
authors.affiliation: Immunoregulation Research Center, Shahed University, Tehran, Iran.
authors.forename: Najmeh
authors.initials: N
authors.lastname: Khojastehnjad
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000628:therapy; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D003131:Combined Modality Therapy; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D000077289:Letrozole; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009570:Nitriles / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000008:administration & dosage; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D000077289:Letrozole; D035683:MicroRNAs; D009570:Nitriles; D013629:Tamoxifen; D014230:Triazoles; C540669:Mirn206 microRNA, mouse; C542687:mirnlet7 microRNA, mouse; C531950:MIRN21 microRNA, mouse
keywords: Exercise training; Letrozole; Tamoxifen; breast cancer; let-7; miR-206; miR-21