Functional Roles of Sex-Biased, Growth Hormone–Regulated MicroRNAs miR-1948 and miR-802 in Young Adult Mouse Liver
Open accessAbstract
Sex-specific temporal patterns of pituitary growth hormone (GH) secretion determine the sex-biased transcription of hundreds of genes in the liver and impart important sex differences in liver physiology, metabolism, and disease. Sex differences in hepatic gene expression vary widely, ranging from less than twofold to >1000-fold in the mouse. Here, we use small RNA sequencing to discover 24 sex-biased mouse liver microRNAs (miRNAs), and then investigate the roles of two of these miRNAs in GH-regulated liver sex differences. Studies in prepubertal and young adult mice, and in mice in which pituitary hormones are ablated or where sex-specific hepatic GH signaling is dysregulated, demonstrated that the male-biased miR-1948 and the female-biased miR-802 are both regulated by sex-specific pituitary GH secretory patterns, acquire sex specificity at puberty, and are dependent on the GH-activated transcription factor STAT5 for their sex-specific expression. Both miRNAs are within genomic regions characterized by sex-biased chromatin accessibility. miR-1948, an uncharacterized miRNA, has essential features for correct Drosha/Dicer processing, generates a bona fide mature miRNA with strong strand bias for the 5p arm, and is bound by Argonaute in liver tissue, as is miR-802. In vivo studies using inhibitory locked nucleic acid sequences revealed that miR-1948-5p preferentially represses female-biased messenger RNAs (mRNAs) and induces male-biased mRNAs in male liver; conversely, miR-802…
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Underpowered data point to a sex-biased miR-21 expression pattern in Neu-AD cells.
“Despite the underpowered data pointing to a sex-biased miR-21 expression pattern in Neu-AD cells, this is not without precedent since the male-dominant expression of miR-21 is already associated with an increased susceptibility to other diseases [117].”
From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [117]
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Most Caenorhabditis elegans microRNAs Are Individually Not Essential for Development or Viability
Miska, E. A., Alvarez-Saavedra, E., Abbott, A. L., Lau, N. C., Hellman, A. B., McGonagle, S. M., Bartel, D. P., Ambros, V. R., & Horvitz, H. R. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030215 · Cited by 484 · see citing works
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Garcia, G., Pinto, S., Ferreira, S., Lopes, D., Serrador, M. J., Fernandes, A., Vaz, A. R., Mendonça, A. D., Edenhofer, F., Malm, T., et al. (2022) · Cells · doi:10.3390/cells11213377 · Cited by 55 · see citing works
“Despite the underpowered data pointing to a sexbiased miR-21 expression pattern in Neu-AD cells, this is not without precedent since the male-dominant expression of miR-21 is already associated with an increased susceptibility to other diseases [117].”
Background
- Authors
- Hao, P., & Waxman, D. J.
- Affiliations
- Boston University (US)
- Corresponding author
- Waxman, David J
- ORCID
- Waxman, David J
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2018-01-16
- Volume
- 159
- Issue
- 3
- Pages
- 1377-1392
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC5839735
- OpenAlex
- W2782775581
- Cited by
- 31
- References
- 1
- Citations by year
- 2025: 1 · 2024: 2 · 2022: 7 · 2021: 7 · 2020: 8 · 2019: 6
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DK033765)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- miR-802, sex-biased gene expression, liver, growth hormone, pituitary gland, STAT5, sex differences, puberty, microRNA biogenesis, Argonaute proteins, cytochrome P450, microRNA target regulation, young adult mice
- MeSH terms
- Animals, Cytochrome P-450 Enzyme System, Female, Gene Expression Regulation, Liver, Male, Mice, Inbred ICR, RNA, Messenger, Sex Characteristics, Growth Hormone, Gene Expression, Mice, Knockout, MicroRNAs, STAT5 Transcription Factor, Mice
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