X-Chromosome-Linked Mir548am-5p is a key regulator of sex disparity in the susceptibility to mitochondria-mediated apoptosis
Open accessAbstract
Sex dimorphism in cell response to stress has previously been investigated by different research groups. This dimorphism could be at least in part accounted for by sex-biased expression of regulatory elements such as microRNAs (miRs). In order to spot previously unknown miR expression differences we took advantage of prior knowledge on specialized databases to identify X chromosome-encoded miRs potentially escaping X chromosome inactivation (XCI). MiR-548am-5p emerged as potentially XCI escaper and was experimentally verified to be significantly up-regulated in human XX primary dermal fibroblasts (DFs) compared to XY ones. Accordingly, miR-548am-5p target mRNAs, e.g. the transcript for Bax, was differently modulated in XX and XY DFs. Functional analyses indicated that XY DFs were more prone to mitochondria-mediated apoptosis than XX ones. Experimentally induced overexpression of miR548am-5p in XY cells by lentivirus vector transduction decreased apoptosis susceptibility, whereas its down-regulation in XX cells enhanced apoptosis susceptibility. These data indicate that this approach could be used to identify previously unreported sex-biased differences in miR expression and that a miR identified with this approach, miR548am-5p, can account for sex-dependent differences observed in the susceptibility to mitochondrial apoptosis of human DFs.
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Sexual dimorphism in mitochondrial function has been related to genetic interactions between sex chromosomes and autosomes.
“Although sexual dimorphism in mitochondrial function have been related to the genetic interactions between sex chromosomes and autosomes (114, 115).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [115]
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From mitochondria to sarcopenia: role of 17β-estradiol and testosterone
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- Authors
- Matarrese, P., Tieri, P., Anticoli, S., Ascione, B., Conte, M., Franceschi, C., Malorni, W., Salvioli, S., & Ruggieri, A.
- Affiliations
- Istituto Superiore di Sanità (IT)
- National Research Council (IT)
- University of Bologna (IT)
- Istituto delle Scienze Neurologiche di Bologna (IT)
- University of Rome Tor Vergata (IT)
- Corresponding author
- Salvioli, Stefano
- Ruggieri, Anna
- ORCID
- Venue
- Cell Death & Disease
- Published
- 2019-09-11
- Volume
- 10
- Issue
- 9
- Pages
- 673-673
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC6739406
- OpenAlex
- W2972597359
- Cited by
- 27
- References
- 58
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 7 · 2020: 8 · 2018: 2
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-11-04)
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Ministero della Salute (RF-2011-02346986)
- Associazione Italiana per la Ricerca sul Cancro (18526)
- Arcobaleno ONLUS
- Peretti Foundation
- Roberto and Cornelia Pallotti's Legacy for Cancer Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Keywords
- sexual dimorphism, X chromosome inactivation escape, mitochondrial apoptosis, dermal fibroblasts, Bax, microRNA expression, apoptosis susceptibility, sex-biased gene expression
- MeSH terms
- Adult, Cells, Cultured, Female, Fibroblasts, Humans, Male, Mitochondria, Sex Characteristics, Down-Regulation, Up-Regulation, Apoptosis, Databases, Genetic, MicroRNAs, Chromosomes, Human, X, Genes, X-Linked
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