MicroRNA-15a finetunes the level of Delta-like 1 homologue (DLK1) in proliferating 3T3-L1 preadipocytes

Ditte C Andersen, Charlotte H Jensen, Mikael Schneider, Anne Yaël Nossent, Tilde Eskildsen, Jakob L Hansen, Børge Teisner, Søren P Sheikh

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: June-10
OriginalsprogEngelsk
TidsskriftExperimental Cell Research
Vol/bind316
Udgave nummer10
Sider (fra-til)1681-1691
ISSN0014-4827
DOI
StatusUdgivet - 10. jun. 2010

Fingeraftryk

MicroRNAs
Cell Size
Membranes
Growth
Cell Cycle Checkpoints
Neoplasms
Peptide Hydrolases
Cell Proliferation
Messenger RNA
Proteins

Citer dette

@article{ea2b20a049fe11df937d000ea68e967b,
title = "MicroRNA-15a finetunes the level of Delta-like 1 homologue (DLK1) in proliferating 3T3-L1 preadipocytes",
abstract = "Delta like 1 homologue (Dlk1) exists in both transmembrane and soluble molecular forms, and is implicated in cellular growth and plays multiple roles in development, tissue regeneration, and cancer. Thus, DLK1 levels are critical for cell function, and abnormal DLK1 expression can be lethal; however, little is known about the underlying mechanisms. We here report that miR-15a modulates DLK1 levels in preadipocytes thus providing a mechanism for DLK1 regulation that further links it to cell cycle arrest and cancer since miR-15a is deregulated in these processes. In preadipocytes, miR-15a increases with cell density, and peaks at the same stage where membrane DLK1(M) and soluble DLK1(S) are found at maximum levels. Remarkably, miR-15a represses the amount of all Dlk1 variants at the mRNA level but also the level of DLK1(M) protein while it increases the amount of DLK1(S) supporting a direct repression of DLK1 and a parallel effect on the protease that cleaves off the DLK1 from the membrane. In agreement with previous studies, we found that miR-15a represses cell numbers, but additionally, we report that miR-15a also increases cell size. Conversely, anti-miR-15a treatment decreases cell size while increasing cell numbers, scenarios that were completely rescued by addition of purified DLK1(S). Our data thus imply that miR-15a regulates cell size and proliferation by fine-tuning Dlk1 among others, and further emphasize miR-15a and DLK1 levels to play important roles in growth signaling networks.",
author = "Andersen, {Ditte C} and Jensen, {Charlotte H} and Mikael Schneider and Nossent, {Anne Ya{\"e}l} and Tilde Eskildsen and Hansen, {Jakob L} and B{\o}rge Teisner and Sheikh, {S{\o}ren P}",
note = "Copyright {\circledC} 2010. Published by Elsevier Inc. Available online 10 April 2010.",
year = "2010",
month = "6",
day = "10",
doi = "10.1016/j.yexcr.2010.04.002",
language = "English",
volume = "316",
pages = "1681--1691",
journal = "Experimental Cell Research",
issn = "0014-4827",
publisher = "Heinemann",
number = "10",

}

MicroRNA-15a finetunes the level of Delta-like 1 homologue (DLK1) in proliferating 3T3-L1 preadipocytes. / Andersen, Ditte C; Jensen, Charlotte H; Schneider, Mikael; Nossent, Anne Yaël; Eskildsen, Tilde; Hansen, Jakob L; Teisner, Børge; Sheikh, Søren P.

I: Experimental Cell Research, Bind 316, Nr. 10, 10.06.2010, s. 1681-1691.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - MicroRNA-15a finetunes the level of Delta-like 1 homologue (DLK1) in proliferating 3T3-L1 preadipocytes

AU - Andersen, Ditte C

AU - Jensen, Charlotte H

AU - Schneider, Mikael

AU - Nossent, Anne Yaël

AU - Eskildsen, Tilde

AU - Hansen, Jakob L

AU - Teisner, Børge

AU - Sheikh, Søren P

N1 - Copyright © 2010. Published by Elsevier Inc. Available online 10 April 2010.

PY - 2010/6/10

Y1 - 2010/6/10

N2 - Delta like 1 homologue (Dlk1) exists in both transmembrane and soluble molecular forms, and is implicated in cellular growth and plays multiple roles in development, tissue regeneration, and cancer. Thus, DLK1 levels are critical for cell function, and abnormal DLK1 expression can be lethal; however, little is known about the underlying mechanisms. We here report that miR-15a modulates DLK1 levels in preadipocytes thus providing a mechanism for DLK1 regulation that further links it to cell cycle arrest and cancer since miR-15a is deregulated in these processes. In preadipocytes, miR-15a increases with cell density, and peaks at the same stage where membrane DLK1(M) and soluble DLK1(S) are found at maximum levels. Remarkably, miR-15a represses the amount of all Dlk1 variants at the mRNA level but also the level of DLK1(M) protein while it increases the amount of DLK1(S) supporting a direct repression of DLK1 and a parallel effect on the protease that cleaves off the DLK1 from the membrane. In agreement with previous studies, we found that miR-15a represses cell numbers, but additionally, we report that miR-15a also increases cell size. Conversely, anti-miR-15a treatment decreases cell size while increasing cell numbers, scenarios that were completely rescued by addition of purified DLK1(S). Our data thus imply that miR-15a regulates cell size and proliferation by fine-tuning Dlk1 among others, and further emphasize miR-15a and DLK1 levels to play important roles in growth signaling networks.

AB - Delta like 1 homologue (Dlk1) exists in both transmembrane and soluble molecular forms, and is implicated in cellular growth and plays multiple roles in development, tissue regeneration, and cancer. Thus, DLK1 levels are critical for cell function, and abnormal DLK1 expression can be lethal; however, little is known about the underlying mechanisms. We here report that miR-15a modulates DLK1 levels in preadipocytes thus providing a mechanism for DLK1 regulation that further links it to cell cycle arrest and cancer since miR-15a is deregulated in these processes. In preadipocytes, miR-15a increases with cell density, and peaks at the same stage where membrane DLK1(M) and soluble DLK1(S) are found at maximum levels. Remarkably, miR-15a represses the amount of all Dlk1 variants at the mRNA level but also the level of DLK1(M) protein while it increases the amount of DLK1(S) supporting a direct repression of DLK1 and a parallel effect on the protease that cleaves off the DLK1 from the membrane. In agreement with previous studies, we found that miR-15a represses cell numbers, but additionally, we report that miR-15a also increases cell size. Conversely, anti-miR-15a treatment decreases cell size while increasing cell numbers, scenarios that were completely rescued by addition of purified DLK1(S). Our data thus imply that miR-15a regulates cell size and proliferation by fine-tuning Dlk1 among others, and further emphasize miR-15a and DLK1 levels to play important roles in growth signaling networks.

U2 - 10.1016/j.yexcr.2010.04.002

DO - 10.1016/j.yexcr.2010.04.002

M3 - Journal article

VL - 316

SP - 1681

EP - 1691

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 10

ER -