Human adipocyte differentiation and composition of disease-relevant lipids are regulated by miR-221-3p.
14-3-3 Proteins
/ genetics
Adipocytes
/ metabolism
Adipogenesis
/ genetics
Adiponectin
/ genetics
Adipose Tissue
/ metabolism
Adult
Aged
Breast Neoplasms
/ genetics
Case-Control Studies
Cell Differentiation
Cell Proliferation
Ceramides
/ classification
Diacylglycerol O-Acyltransferase
/ genetics
Fatty Acid-Binding Proteins
/ genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Lipase
/ genetics
Lipid Droplets
/ metabolism
MCF-7 Cells
Mammary Glands, Human
/ metabolism
MicroRNAs
/ agonists
Middle Aged
Signal Transduction
Sphingolipids
/ classification
Stearoyl-CoA Desaturase
/ genetics
Triglycerides
/ classification
fas Receptor
/ genetics
Adipose tissue
Breast cancer
Lipid storage
Lipogenesis
Sphingolipid
microRNA
Journal
Biochimica et biophysica acta. Molecular and cell biology of lipids
ISSN: 1879-2618
Titre abrégé: Biochim Biophys Acta Mol Cell Biol Lipids
Pays: Netherlands
ID NLM: 101731727
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
05
08
2020
revised:
07
10
2020
accepted:
11
10
2020
pubmed:
20
10
2020
medline:
14
4
2021
entrez:
19
10
2020
Statut:
ppublish
Résumé
MicroRNA-221-3p (miR-221-3p) is associated with both metabolic diseases and cancers. However, its role in terminal adipocyte differentiation and lipid metabolism are uncharacterized. miR-221-3p or its inhibitor was transfected into differentiating or mature human adipocytes. Triglyceride (TG) content and adipogenic gene expression were monitored, global lipidome analysis was carried out, and mechanisms underlying the effects of miR-221-3p were investigated. Finally, cross-talk between miR-221-3p expressing adipocytes and MCF-7 breast carcinoma (BC) cells was studied, and miR-221-3p expression in tumor-proximal adipose biopsies from BC patients analyzed. miR-221-3p overexpression inhibited terminal differentiation of adipocytes, as judged from reduced TG storage and gene expression of the adipogenic markers SCD1, GLUT4, FAS, DGAT1/2, AP2, ATGL and AdipoQ, whereas the miR-221-3p inhibitor increased TG storage. Knockdown of the predicted miR-221-3p target, 14-3-3γ, had similar antiadipogenic effects as miR-221-3p overexpression, indicating it as a potential mediator of mir-221-3p function. Importantly, miR-221-3p overexpression inhibited de novo lipogenesis but increased the concentrations of ceramides and sphingomyelins, while reducing diacylglycerols, concomitant with suppression of sphingomyelin phosphodiesterase, ATP citrate lyase, and acid ceramidase. miR-221-3p expression was elevated in tumor proximal adipose tissue from patients with invasive BC. Conditioned medium of miR-221-3p overexpressing adipocytes stimulated the invasion and proliferation of BC cells, while medium of the BC cells enhanced miR-221-3p expression in adipocytes. Elevated miR-221-3p impairs adipocyte lipid storage and differentiation, and modifies their ceramide, sphingomyelin, and diacylglycerol content. These alterations are relevant for metabolic diseases but may also affect cancer progression.
Identifiants
pubmed: 33075494
pii: S1388-1981(20)30233-X
doi: 10.1016/j.bbalip.2020.158841
pii:
doi:
Substances chimiques
14-3-3 Proteins
0
ADIPOQ protein, human
0
Adiponectin
0
Ceramides
0
FABP4 protein, human
0
FAS protein, human
0
Fatty Acid-Binding Proteins
0
MIRN221 microRNA, human
0
MicroRNAs
0
Sphingolipids
0
Triglycerides
0
YWHAG protein, human
0
fas Receptor
0
SCD1 protein, human
EC 1.14.19.1
Stearoyl-CoA Desaturase
EC 1.14.19.1
DGAT1 protein, human
EC 2.3.1.20
DGAT2 protein, human
EC 2.3.1.20
Diacylglycerol O-Acyltransferase
EC 2.3.1.20
Lipase
EC 3.1.1.3
PNPLA2 protein, human
EC 3.1.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
158841Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.