MicroRNA-15a fine-tunes the level of Delta-like 1 homolog (DLK1) in proliferating 3T3-L1 preadipocytes - PubMed (original) (raw)
. 2010 Jun 10;316(10):1681-91.
doi: 10.1016/j.yexcr.2010.04.002. Epub 2010 Apr 10.
Affiliations
- PMID: 20385127
- DOI: 10.1016/j.yexcr.2010.04.002
MicroRNA-15a fine-tunes the level of Delta-like 1 homolog (DLK1) in proliferating 3T3-L1 preadipocytes
Ditte C Andersen et al. Exp Cell Res. 2010.
Abstract
Delta like 1 homolog (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.
Copyright 2010 Elsevier Inc. All rights reserved.
Similar articles
- dlk1 specifically interacts with insulin-like growth factor binding protein 1 to modulate adipogenesis of 3T3-L1 cells.
Nueda ML, García-Ramírez JJ, Laborda J, Baladrón V. Nueda ML, et al. J Mol Biol. 2008 Jun 6;379(3):428-42. doi: 10.1016/j.jmb.2008.03.070. Epub 2008 Apr 7. J Mol Biol. 2008. PMID: 18466921 - The novel gene EGFL9/Dlk2, highly homologous to Dlk1, functions as a modulator of adipogenesis.
Nueda ML, Baladrón V, García-Ramírez JJ, Sánchez-Solana B, Ruvira MD, Rivero S, Ballesteros MA, Monsalve EM, Díaz-Guerra MJ, Ruiz-Hidalgo MJ, Laborda J. Nueda ML, et al. J Mol Biol. 2007 Apr 13;367(5):1270-80. doi: 10.1016/j.jmb.2006.10.020. Epub 2006 Oct 13. J Mol Biol. 2007. PMID: 17320102 - PU.1 promotes miR-191 to inhibit adipogenesis in 3T3-L1 preadipocytes.
Ji S, Li W, Bao L, Han P, Yang W, Ma L, Meng F, Cao B. Ji S, et al. Biochem Biophys Res Commun. 2014 Aug 22;451(2):329-33. doi: 10.1016/j.bbrc.2014.07.130. Epub 2014 Aug 2. Biochem Biophys Res Commun. 2014. PMID: 25094047 - miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression.
Kim SY, Kim AY, Lee HW, Son YH, Lee GY, Lee JW, Lee YS, Kim JB. Kim SY, et al. Biochem Biophys Res Commun. 2010 Feb 12;392(3):323-8. doi: 10.1016/j.bbrc.2010.01.012. Epub 2010 Jan 7. Biochem Biophys Res Commun. 2010. PMID: 20060380 - The imprinted gene Delta like non-canonical Notch ligand 1 (Dlk1) is conserved in mammals, and serves a growth modulatory role during tissue development and regeneration through Notch dependent and independent mechanisms.
Traustadóttir GÁ, Lagoni LV, Ankerstjerne LBS, Bisgaard HC, Jensen CH, Andersen DC. Traustadóttir GÁ, et al. Cytokine Growth Factor Rev. 2019 Apr;46:17-27. doi: 10.1016/j.cytogfr.2019.03.006. Epub 2019 Mar 23. Cytokine Growth Factor Rev. 2019. PMID: 30930082 Review.
Cited by
- Expression profiling of preadipocyte microRNAs by deep sequencing on chicken lines divergently selected for abdominal fatness.
Wang W, Du ZQ, Cheng B, Wang Y, Yao J, Li Y, Cao Z, Luan P, Wang N, Li H. Wang W, et al. PLoS One. 2015 Feb 12;10(2):e0117843. doi: 10.1371/journal.pone.0117843. eCollection 2015. PLoS One. 2015. PMID: 25675096 Free PMC article. - Role of microRNAs in obesity and obesity-related diseases.
Iacomino G, Siani A. Iacomino G, et al. Genes Nutr. 2017 Sep 25;12:23. doi: 10.1186/s12263-017-0577-z. eCollection 2017. Genes Nutr. 2017. PMID: 28974990 Free PMC article. Review. - MiRNA-181a regulates adipogenesis by targeting tumor necrosis factor-α (TNF-α) in the porcine model.
Li H, Chen X, Guan L, Qi Q, Shu G, Jiang Q, Yuan L, Xi Q, Zhang Y. Li H, et al. PLoS One. 2013 Oct 1;8(10):e71568. doi: 10.1371/journal.pone.0071568. eCollection 2013. PLoS One. 2013. PMID: 24098322 Free PMC article. - Weight-reduction through a low-fat diet causes differential expression of circulating microRNAs in obese C57BL/6 mice.
Hsieh CH, Rau CS, Wu SC, Yang JC, Wu YC, Lu TH, Tzeng SL, Wu CJ, Lin CW. Hsieh CH, et al. BMC Genomics. 2015 Sep 16;16(1):699. doi: 10.1186/s12864-015-1896-3. BMC Genomics. 2015. PMID: 26377847 Free PMC article. - Regulation of Adipocyte Differentiation via MicroRNAs.
Son YH, Ka S, Kim AY, Kim JB. Son YH, et al. Endocrinol Metab (Seoul). 2014 Jun;29(2):122-35. doi: 10.3803/EnM.2014.29.2.122. Endocrinol Metab (Seoul). 2014. PMID: 25031884 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources