PLIN2 Functions As a Novel Link Between Progesterone Signaling and Metabolism in Uterine Leiomyoma Cells.
Adult
Biomarkers, Tumor
/ genetics
Case-Control Studies
Cell Proliferation
Female
Follow-Up Studies
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Glycolysis
Humans
Leiomyoma
/ genetics
Metabolome
Myometrium
/ metabolism
Perilipin-2
/ antagonists & inhibitors
Progesterone
/ metabolism
Prognosis
RNA, Small Interfering
Receptors, Progesterone
/ genetics
Signal Transduction
Uterine Neoplasms
/ genetics
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
01 12 2019
01 12 2019
Historique:
received:
04
04
2019
accepted:
16
07
2019
pubmed:
11
9
2019
medline:
5
6
2020
entrez:
11
9
2019
Statut:
ppublish
Résumé
Uterine leiomyoma (fibroids) are the most common tumors in women. Recently, perilipin-2 (PLIN2) was identified as a critical target gene of the progesterone receptor; however, its function in the pathogenesis of fibroids is unknown. To determine the function of PLIN2 in leiomyoma cells. Tissue and primary cells from leiomyoma and myometrium were analyzed. PLIN2 function in leiomyoma was assessed using small interfering RNA. RNA-sequencing was performed to identify genome-wide effects of PLIN2 depletion. Metabolic activity was measured using the Seahorse XF96 analyzer. Real-time quantitative PCR and immunoblotting were also performed. Laboratory. Forty-one premenopausal women undergoing surgery for fibroids. Gene expression, oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and cell proliferation. PLIN2 gene expression was 2.4-fold lower in leiomyoma compared with adjacent myometrium, suggesting a link between PLIN2 deficiency and fibroids. A total of 3877 genes were differentially expressed after PLIN2 knockdown. Gene ontology analysis identified metabolism as the second-highest biological process affected by PLIN2 depletion. OCR (mitochondrial respiration) and ECAR (glycolysis) were significantly upregulated after PLIN2 knockdown; PLIN2-depleted cells had a greater basal metabolic activity and higher metabolic stress response. Cell proliferation was also significantly increased after PLIN2 knockdown. PLIN2 depletion increases mitochondrial respiration and glycolysis, suggesting that PLIN2 is a critical regulator of metabolic function in leiomyoma cells. PLIN2 deficiency also reprograms leiomyoma cells to a proproliferative phenotype. These findings introduce metabolomics as an area to explore to better understand leiomyoma tumorigenesis.
Identifiants
pubmed: 31504629
pii: 5536619
doi: 10.1210/jc.2019-00762
pmc: PMC6823729
doi:
Substances chimiques
Biomarkers, Tumor
0
PLIN2 protein, human
0
Perilipin-2
0
RNA, Small Interfering
0
Receptors, Progesterone
0
Progesterone
4G7DS2Q64Y
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
6256-6264Subventions
Organisme : NICHD NIH HHS
ID : P01 HD057877
Pays : United States
Informations de copyright
Copyright © 2019 Endocrine Society.
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