Androgen-dependent miR-125a-5p targets LYPLA1 and regulates global protein palmitoylation level in late-onset hypogonadism males.
J Cell Physiol
; 236(6): 4738-4749, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33284463
ABSTRACT
Late-onset hypogonadism (LOH) is defined as a clinical and biochemical syndrome with multiple symptoms caused by testosterone deficiency in aging males. An in-depth exploration of the molecular mechanism underlying LOH development is insufficient. We previously identified miR-125a-5p as a dysregulated microRNA in LOH patients and potential diagnostic biomarker for LOH. The present study demonstrated that plasma miR-125a-5p was upregulated after testosterone supplementation in both LOH patients and castrated mice, and positively associated with the testosterone concentrations, suggesting direct regulation of miR-125a-5p expression by testosterone. Androgen response element in the promoter of miR-125a-5p was subsequently identified. Target gene screening and confirmation verified that LYPLA1, encoding acyl-protein thioesterase 1 which catalyzed protein depalmitoylation process, was a target gene of miR-125a-5p. Furthermore, in cells cultured with testosterone deprivation and organs from castrated mice, testosterone deficiency led to decreased global protein palmitoylation level. In aging males, global protein palmitoylation in peripheral blood showed a notable decline in LOH patients contrast to the normal elderly males. And the palmitoylation level was positively correlative with serum testosterone concentrations. Our results suggested that testosterone could regulate global palmitoylation level through miR-125a-5p/LYPLA1 signaling pathway. Given that protein palmitoylation is pivotal for protein function and constitutes the pathogenesis of various diseases, testosterone/miR-125a-5p/LYPLA1 may contribute to the molecular mechanism underlying multiple symptoms caused by testosterone deficiency in LOH patients, and aberrant global palmitoylation could be a potential biomarker for LOH.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Testosterona
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Tioléster Hidrolases
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Processamento de Proteína Pós-Traducional
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MicroRNAs
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Lipoilação
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Hipogonadismo
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Animals
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China