The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
MicroRNA-21 Is a Downstream Effector of AKT That Mediates Its Antiapoptotic Effects via Suppression of Fas Ligand
Open accessAbstract
MicroRNA-21 (miR-21) is highly up-regulated during hypertrophic and cancerous cell growth. In contrast, we found that it declines in cardiac myocytes upon exposure to hypoxia. Thus, the objective was to explore its role during hypoxia. We show that miR-21 not only regulates phosphatase and tensin homologue deleted on chromosome 10 (PTEN), but also targets Fas ligand (FasL). During prolonged hypoxia, down-regulation of miR-21 proved necessary and sufficient for enhancing expression of both proteins. We demonstrate here for the first time that miR-21 is positively regulated via an AKT-dependent pathway, which is depressed during prolonged hypoxia. Accordingly, hypoxia-induced down-regulation of miR-21 and up-regulation of FasL and PTEN were reversed by activated AKT and reproduced by a dominant negative mutant, wortmannin, or PTEN. Moreover, the antiapoptotic function of AKT partly required miR-21, which was sufficient for inhibition of caspase-8 activity and mitochondrial damage. In consensus, overexpression of miR-21 in a transgenic mouse heart resulted in suppression of ischemia-induced up-regulation of PTEN and FasL expression, an increase in phospho-AKT, a smaller infarct size, and ameliorated heart failure. Thus, we have identified a unique aspect of the function of AKT by which it inhibits apoptosis through miR-21-dependent suppression of FasL.
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Cites
MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
Thum, T., Gross, C., Fiedler, J., Fischer, T., Kissler, S., Bussen, M., Galuppo, P., Just, S., Rottbauer, W., Frantz, S., et al. (2008) · Nature · doi:10.1038/nature07511 · Cited by 2,349
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Packer, A. N., Xing, Y., Harper, S. Q., Jones, L., & Davidson, B. L. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2390-08.2008 · Cited by 679
Dong, S., Cheng, Y., Yang, J., Li, J., Liu, X., Wang, X., Wang, D., Krall, T. J., Delphin, E. S., & Zhang, C. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.027896 · Cited by 454
Stiles, B., Wang, Y., Stahl, A., Bassilian, S., Lee, W. P., Kim, Y.-J., Sherwin, R., Devaskar, S., Lesche, R., Magnuson, M. A., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308617100 · Cited by 436
MicroRNA-21 protects against the H2O2-induced injury on cardiac myocytes via its target gene PDCD4
Cheng, Y., Liu, X., Zhang, S., Lin, Y., Yang, J., & Zhang, C. (2009) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2009.01.008 · Cited by 368
MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths
Sayed, D., Rane, S., Lypowy, J., He, M., Chen, I.-Y., Vashistha, H., Yan, L., Malhotra, A., Vatner, D., & Abdellatif, M. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-02-0159 · Cited by 355
Self-citationTranslation Inhibitor Pdcd4 Is Targeted for Degradation during Tumor Promotion
Schmid, T., Jansen, A. P., Baker, A. R., Hegamyer, G., Hagan, J. P., & Colburn, N. H. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-1719 · Cited by 151
Cited by
Aging of the musculoskeletal system: How the loss of estrogen impacts muscle strength
Collins, B. C., Laakkonen, E. K., & Lowe, D. A. (2019) · Bone · doi:10.1016/j.bone.2019.03.033 · Cited by 227
“While HSP’s were not measured, miR-146a has been implicated in regulating the immune response by targeting cytokine production, such as TNF-α and FasL [80].”
ResultInfluentialResveratrol Reduces Prostate Cancer Growth and Metastasis by Inhibiting the Akt/MicroRNA-21 Pathway
Sheth, S., Jajoo, S., Kaur, T., Mukherjea, D., Sheehan, K., Rybak, L. P., & Ramkumar, V. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051655 · Cited by 225
Targeting miR-21 Inhibits In Vitro and In Vivo Multiple Myeloma Cell Growth
Leone, E., Morelli, E., Di Martino, M. T., Amodio, N., Foresta, U., Gullà, A., Rossi, M., Neri, A., Giordano, A., Munshi, N. C., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3325 · Cited by 219
Abels, E. R., Maas, S. L. N., Nieland, L., Wei, Z., Cheah, P. S., Tai, E., Kolsteeg, C.-J., Dusoswa, S. A., Ting, D. T., Hickman, S., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.036 · Cited by 199
Hypoxia-regulated microRNAs in human cancer
Shen, G., Li, X., Jia, Y.-F., Piazza, G. A., & Xi, Y. (2013) · Acta Pharmacologica Sinica · doi:10.1038/aps.2012.195 · Cited by 164
Metadata
- Authors
- Sayed, D., He, M., Hong, C., Gao, S., Rane, S., Yang, Z., & Abdellatif, M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 285
- Issue
- 26
- Pages
- 20281-20290
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1963640511
- Cited by
- 315
- References
- 10
- FWCI
- 9.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Sayed, D., He, M., Hong, C., Gao, S., Rane, S., Yang, Z., & Abdellatif, M. (2010). MicroRNA-21 Is a Downstream Effector of AKT That Mediates Its Antiapoptotic Effects via Suppression of Fas Ligand. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m110.109207
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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