Research Papers:

Menopause and adipose tissue: miR-19a-3p is sensitive to hormonal replacement

Reeta Kangas, Cristina Morsiani _, Grazia Pizza, Catia Lanzarini, Pauliina Aukee, Jaakko Kaprio, Sarianna Sipilä, Claudio Franceschi, Vuokko Kovanen, Eija K. Laakkonen and Miriam Capri

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Oncotarget. 2018; 9:2279-2294. https://doi.org/10.18632/oncotarget.23406

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Reeta Kangas1,*, Cristina Morsiani2,*, Grazia Pizza2,3, Catia Lanzarini2, Pauliina Aukee4, Jaakko Kaprio5, Sarianna Sipilä1, Claudio Franceschi2, Vuokko Kovanen1, Eija K. Laakkonen1 and Miriam Capri2,6

1Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland

2DIMES-Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy

3Epigenetics Program, Babraham Institute, Cambridge, United Kingdom

4Department of Obstetrics and Gynecology, Pelvic Floor Research and Therapy Unit, Central Finland Central Hospital, Jyväskylä, Finland

5Institute for Molecular Medicine Finland (FIMM) and Department of Public Health, University of Helsinki, Helsinki, Finland

6CIG- Interdepartmental Centre “Galvani”, Via Petronio Vecchi, University of Bologna, Bologna, Italy

*These authors have contributed equally to this work

Correspondence to:

Cristina Morsiani, email: [email protected]

Keywords: microRNAs; miR-19a-3p; adipose tissue; aging; estrogen therapy

Abbreviations: ESR1: estrogen receptor 1; AKT1: AKT serine/threonine kinase 1; BRAF: B-Raf proto-oncogene, serine/threonine kinase; BCL-2: B-cell lymphoma 2; CCND1: cyclin D1

Received: August 06, 2017    Accepted: December 04, 2017    Published: December 18, 2017


Tissue-specific effects of 17β-estradiol are delivered via both estrogen receptors and microRNAs (miRs). Menopause is known to affect the whole-body fat distribution in women. This investigation aimed at identifying menopause- and hormone replacement therapy (HRT)-associated miR profiles and miR targets in subcutaneous abdominal adipose tissue and serum from the same women. A discovery phase using array technology was performed in 13 women, including monozygotic twin pairs discordant for HRT and premenopausal young controls. Seven miRs, expressed in both adipose tissue and serum, were selected for validation phase in 34 women from a different cohort. An age/menopause-related increase of miRs-16-5p, -451a, -223-3p, -18a-5p, -19a-3p,-486-5p and -363-3p was found in the adipose tissue, but not in serum. MiR-19a-3p, involved in adipocyte development and estrogen signaling, resulted to be higher in HRT users in comparison with non-users. Among the identified targets, AKT1, BCL-2 and BRAF proteins showed lower expression in both HRT and No HRT users in comparison with premenopausal women. Unexpectedly, ESR1 protein expression was not modified although its mRNA was lower in No HRT users compared to premenopausal women and HRT users. Thus, both HRT and menopause appear to affect adipose tissue homeostasis via miR-mediated mechanism.

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