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Androgen-dependent miR-125a-5p targets LYPLA1 and regulates global protein palmitoylation level in late-onset hypogonadism males
- Source :
- Journal of cellular physiologyREFERENCES. 236(6)
- Publication Year :
- 2020
-
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.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Physiology
Hormone Replacement Therapy
Lipoylation
Clinical Biochemistry
Biology
Response Elements
PC12 Cells
Pathogenesis
03 medical and health sciences
0302 clinical medicine
Palmitoylation
Downregulation and upregulation
Internal medicine
Protein depalmitoylation
medicine
Animals
Humans
Protein palmitoylation
Testosterone
Castration
Promoter Regions, Genetic
Aged
Hypogonadism
Age Factors
Cell Biology
Middle Aged
Rats
Mice, Inbred C57BL
Disease Models, Animal
MicroRNAs
030104 developmental biology
Endocrinology
HEK293 Cells
030220 oncology & carcinogenesis
Case-Control Studies
Thiolester Hydrolases
Signal transduction
Androgen Response Element
Protein Processing, Post-Translational
Subjects
Details
- ISSN :
- 10974652
- Volume :
- 236
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of cellular physiologyREFERENCES
- Accession number :
- edsair.doi.dedup.....25f870918781fdcae2231cb896642d4d