BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

MicroRNA let-7c inhibits Bcl-xl expression and regulates ox-LDL-induced endothelial apoptosis

  • Qin, Bing (Department of Neurology, Xiangya Hospital, Central South University) ;
  • Xiao, Bo (Department of Neurology, Xiangya Hospital, Central South University) ;
  • Liang, Desheng (State Key Laboratory of Medical Genetics, Central South University) ;
  • Li, Ye (Department of Neurology, Xiangya Hospital, Central South University) ;
  • Jiang, Ting (Department of Neurology, Xiangya Hospital, Central South University) ;
  • Yang, Huan (Department of Neurology, Xiangya Hospital, Central South University)
  • Received : 2012.02.14
  • Accepted : 2012.05.24
  • Published : 2012.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

Endothelial cells (ECs) apoptosis induced by oxidized low-density lipoprotein (ox-LDL) is thought to play a critical role in atherosclerosis. MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in diverse cell functions, including differentiation, growth, proliferation, and apoptosis. MiRNA let-7 family is known to be involved in the regulation of cell apoptosis. However, the function of let-7 in ox-LDL induced ECs apoptosis and atherosclerosis is still unknown. Here, we show that let-7c expression was markedly up-regulated in ox-LDL induced apoptotic human umbilical cord vein endothelial cells (HUVECs). Let-7c over-expression enhanced apoptosis in ECs whereas inhibition of let-7c could partly alleviate apoptotic cell death mediated by ox-LDL. Searching for how let-7c affected apoptosis, we discovered that antiapoptotic protein Bcl-xl was a direct target of let-7c in ECs. Our data suggest that let-7c contributes to endothelial apoptosis through suppression of Bcl-xl.

Keywords

References

  1. Wang, N., Han, Y., Tao, J., Huang, M., You, Y., Zhang, H., Liu, S., Zhang, X. and Yan, C. (2011) Overexpression of CREG attenuates atherosclerotic endothelium apoptosis via VEGF/PI3K/AKT pathway. Atherosclerosis 218, 543-551. https://doi.org/10.1016/j.atherosclerosis.2011.08.002
  2. Borradaile, N. M. and Pickering, J. G. (2010) Polyploidy impairs human aortic endothelial cell function and is prevented by nicotinamide phosphoribosyltransferase. Am. J. Physiol. Cell Physiol. 298, C66-74. https://doi.org/10.1152/ajpcell.00357.2009
  3. Libby, P. (2002) Inflammation in atherosclerosis. Nature 420, 868-874. https://doi.org/10.1038/nature01323
  4. Choy, J. C., Granville, D. J., Hunt, D. W. and McManus, B. M. (2001) Endothelial cell apoptosis: biochemical characteristics and potential implications for atherosclerosis. J. Mol. Cell Cardiol. 33, 1673-1690. https://doi.org/10.1006/jmcc.2001.1419
  5. Zhang, L., Sivashanmugam, P., Wu, J. H., Brian, L., Exum, S. T., Freedman, N. J. and Peppel, K. (2008) Tumor necrosis factor receptor-2 signaling attenuates vein graft neointima formation by promoting endothelial recovery. Arterioscler. Thromb. Vasc. Biol. 28, 284-289.
  6. von Eckardstein, A. and Rohrer, L. (2009) Transendothelial lipoprotein transport and regulation of endothelial permeability and integrity by lipoproteins. Curr. Opin. Lipidol. 20, 197-205. https://doi.org/10.1097/MOL.0b013e32832afd63
  7. Zhang, L., Zhou, G., Song, W., Tan, X., Guo, Y., Zhou, B., Jing, H., Zhao, S. and Chen, L. (2012) Pterostilbene protects vascular endothelial cells against oxidized low-density lipoprotein-induced apoptosis in vitro and in vivo. Apoptosis. 17, 25-36. https://doi.org/10.1007/s10495-011-0653-6
  8. Ross, R. (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362, 801-809. https://doi.org/10.1038/362801a0
  9. Zhang, X., Hu, K. and Li, C. Y. (2001) Protection against oxidized low-density lipoprotein-induced vascular endothelial cell death by integrin-linked kinase. Circulation 104, 2762-2766. https://doi.org/10.1161/hc4801.100792
  10. Lu, J., Yang, J. H., Burns, A. R., Chen, H. H., Tang, D., Walterscheid, J. P., Suzuki, S., Yang, C. Y., Sawamura, T. and Chen, C. H. (2009) Mediation of electronegative low-density lipoprotein signaling by LOX-1: a possible mechanism of endothelial apoptosis. Circ. Res. 104, 619-627. https://doi.org/10.1161/CIRCRESAHA.108.190116
  11. Lee, Y. H., Mungunsukh, O., Tutino, R. L., Marquez, A. P. and Day, R. M. (2010) Angiotensin-II-induced apoptosis requires regulation of nucleolin and Bcl-xL by SHP-2 in primary lung endothelial cells. J. Cell Sci. 123, 1634-1643. https://doi.org/10.1242/jcs.063545
  12. D'Amelio, M., Cavallucci, V. and Cecconi, F. (2010) Neuronal caspase-3 signaling: not only cell death. Cell Death. Differ. 17, 1104-1114. https://doi.org/10.1038/cdd.2009.180
  13. Pan, Y., Guo, M., Nie, Z., Huang, Y., Peng, Y., Liu, A., Qing, M. and Yao, S. (2012) Colorimetric detection of apoptosis based on caspase-3 activity assay using unmodified gold nanoparticles. Chem. Commun. (Camb) 48, 997-999. https://doi.org/10.1039/c1cc15407a
  14. Bartel, D. P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297. https://doi.org/10.1016/S0092-8674(04)00045-5
  15. Filipowicz, W., Bhattacharyya, S. N. and Sonenberg, N. (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat. Rev. Genet. 9, 102-114.
  16. Urbich, C., Kuehbacher, A. and Dimmeler, S. (2008) Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc. Res. 79, 581-588. https://doi.org/10.1093/cvr/cvn156
  17. Poliseno, L., Tuccoli, A., Mariani, L., Evangelista, M., Citti, L., Woods, K., Mercatanti, A., Hammond, S. and Rainaldi, G. (2006) MicroRNAs modulate the angiogenic properties of HUVECs. Blood 108, 3068-3071. https://doi.org/10.1182/blood-2006-01-012369
  18. Li, Y. X., Liu, D. Q., Zheng, C., Zheng, S. Q., Liu, M., Li, X. and Tang, H. (2011) miR-200a modulate HUVECs viability and migration. IUBMB Life. 63, 553-559. https://doi.org/10.1002/iub.486
  19. Rippe, C., Blimline, M., Magerko, K. A., Lawson, B. R., Larocca, T., Donato, A. J. and Seals, D. R. (2012) MicroRNA changes in human arterial endothelial cells with senescence: Relation to apoptosis, eNOS and inflammation. Exp. Gerontol. 47, 45-51. https://doi.org/10.1016/j.exger.2011.10.004
  20. Ruan, W., Xu, J. M., Li, S. B., Yuan, L. Q. and Dai, R. P. (2012) Effects of down-regulation of microRNA-23a on TNF-alpha- induced endothelial cell apoptosis through caspase-dependent pathways. Cardiovasc. Res. 93, 623-632. https://doi.org/10.1093/cvr/cvr290
  21. Lagos-Quintana, M., Rauhut, R., Lendeckel, W. and Tuschl, T. (2001) Identification of novel genes coding for small expressed RNAs. Science 294, 853-858. https://doi.org/10.1126/science.1064921
  22. Boyerinas, B., Park, S. M., Hau, A., Murmann, A. E. and Peter, M. E. (2010) The role of let-7 in cell differentiation and cancer. Endocr. Relat. Cancer 17, F19-36. https://doi.org/10.1677/ERC-09-0184
  23. Qin, B., Xiao, B., Liang, D., Xia, J., Li, Y. and Yang, H. (2011) MicroRNAs expression in ox-LDL treated HUVECs: MiR-365 modulates apoptosis and Bcl-2 expression. Biochem. Biophys. Res. Commun. 410, 127-133. https://doi.org/10.1016/j.bbrc.2011.05.118
  24. Shimizu, S., Takehara, T., Hikita, H., Kodama, T., Miyagi, T., Hosui, A., Tatsumi, T., Ishida, H., Noda, T., Nagano, H., Doki, Y., Mori, M. and Hayashi, N. (2010) The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib- induced apoptosis in human hepatocellular carcinoma. J. Hepatol. 52, 698-704. https://doi.org/10.1016/j.jhep.2009.12.024
  25. Wang, X., Zhou, Y., Kim, H. P., Song, R., Zarnegar, R., Ryter, S. W. and Choi, A. M. (2004) Hepatocyte growth factor protects against hypoxia/reoxygenation-induced apoptosis in endothelial cells. J. Biol. Chem. 279, 5237-5243. https://doi.org/10.1074/jbc.M309271200
  26. Ghosh, G., Subramanian, I. V., Adhikari, N., Zhang, X., Joshi, H. P., Basi, D., Chandrashekhar, Y. S., Hall, J. L., Roy, S., Zeng, Y. and Ramakrishnan, S. (2010) Hypoxia-induced microRNA- 424 expression in human endothelial cells regulates HIF-alpha isoforms and promotes angiogenesis. J. Clin. Invest. 120, 4141-4154. https://doi.org/10.1172/JCI42980
  27. Kuhnert, F. and Kuo, C. J. (2010) miR-17-92 angiogenesis micromanagement. Blood 115, 4631-4633. https://doi.org/10.1182/blood-2010-03-276428
  28. Suarez, Y., Fernandez-Hernando, C., Pober, J. S. and Sessa, W. C. (2007) Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ. Res. 100, 1164-1173. https://doi.org/10.1161/01.RES.0000265065.26744.17
  29. Staszel, T., Zapala, B., Polus, A., Sadakierska-Chudy, A., Kiec-Wilk, B., Stepien, E., Wybranska, I., Chojnacka, M. and Dembinska-Kiec, A. (2011) Role of microRNAs in endothelial cell pathophysiology. Pol. Arch. Med. Wewn 121, 361-367.
  30. Yang, B. F., Lu, Y. J. and Wang, Z. G. (2009) MicroRNAs and apoptosis: implications in the molecular therapy of human disease. Clin. Exp. Pharmacol. Physiol. 36, 951-960. https://doi.org/10.1111/j.1440-1681.2009.05245.x
  31. Vecchione, A. and Croce, C. M. (2010) Apoptomirs: small molecules have gained the license to kill. Endocr. Relat. Cancer 17, F37-50. https://doi.org/10.1677/ERC-09-0163
  32. Peter, M. E. (2009) Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle. 8, 843-852. https://doi.org/10.4161/cc.8.6.7907
  33. Zhou, F., Yang, Y. and Xing, D. (2011) Bcl-2 and Bcl-xL play important roles in the crosstalk between autophagy and apoptosis. FEBS J. 278, 403-413. https://doi.org/10.1111/j.1742-4658.2010.07965.x
  34. Grad, J. M., Zeng, X. R. and Boise, L. H. (2000) Regulation of Bcl-xL: a little bit of this and a little bit of STAT. Curr. Opin. Oncol. 12, 543-549. https://doi.org/10.1097/00001622-200011000-00006
  35. Dhanabal, M., Ramchandran, R., Waterman, M. J., Lu, H., Knebelmann, B., Segal, M. and Sukhatme, V. P. (1999) Endostatin induces endothelial cell apoptosis. J. Biol. Chem. 274, 11721-11726. https://doi.org/10.1074/jbc.274.17.11721
  36. Li, C., Issa, R., Kumar, P., Hampson, I. N., Lopez-Novoa, J. M., Bernabeu, C. and Kumar, S. (2003) CD105 prevents apoptosis in hypoxic endothelial cells. J. Cell Sci. 116, 2677-2685. https://doi.org/10.1242/jcs.00470
  37. Fuchsluger, T. A., Jurkunas, U., Kazlauskas, A. and Dana, R. (2011) Anti-apoptotic gene therapy prolongs survival of corneal endothelial cells during storage. Gene Ther. 18, 778-787. https://doi.org/10.1038/gt.2011.20
  38. Chen, X. P., Xun, K. L., Wu, Q., Zhang, T. T., Shi, J. S. and Du, G. H. (2007) Oxidized low density lipoprotein receptor-1 mediates oxidized low density lipoprotein-induced apoptosis in human umbilical vein endothelial cells: role of reactive oxygen species. Vascul. Pharmacol. 47, 1-9. https://doi.org/10.1016/j.vph.2007.01.004

Cited by

  1. MicroRNA modulation of lipid metabolism and oxidative stress in cardiometabolic diseases vol.64, 2013, https://doi.org/10.1016/j.freeradbiomed.2013.07.014
  2. Regulation of autophagy and apoptosis in response to ox-LDL in vascular smooth muscle cells, and the modulatory effects of the microRNA hsa-let-7g vol.168, pp.2, 2013, https://doi.org/10.1016/j.ijcard.2012.12.045
  3. Targeting of p53 peptide analogues to anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy vol.443, pp.3, 2014, https://doi.org/10.1016/j.bbrc.2013.12.054
  4. MicroRNA-133a and microRNA-326 co-contribute to hepatocellular carcinoma 5-fluorouracil and cisplatin sensitivity by directly targeting B-cell lymphoma-extra large vol.12, pp.4, 2015, https://doi.org/10.3892/mmr.2015.4134
  5. Epithelial and Stromal MicroRNA Signatures of Columnar Cell Hyperplasia Linking Let-7c to Precancerous and Cancerous Breast Cancer Cell Proliferation vol.9, pp.8, 2014, https://doi.org/10.1371/journal.pone.0105099
  6. Novel integrative genomic tool for interrogating lithium response in bipolar disorder vol.5, pp.2, 2015, https://doi.org/10.1038/tp.2014.139
  7. Redox regulation of microRNAs in endometriosis-associated pain vol.12, 2017, https://doi.org/10.1016/j.redox.2017.04.037
  8. MiR-448 promotes vascular smooth muscle cell proliferation and migration in through directly targeting MEF2C 2017, https://doi.org/10.1007/s11356-017-9771-1
  9. Circulating miR-155, miR-145 and let-7c as diagnostic biomarkers of the coronary artery disease vol.7, 2017, https://doi.org/10.1038/srep42916
  10. Expression profile of microRNAs in gastrointestinal stromal tumors revealed by high throughput quantitative RT-PCR microarray vol.21, pp.19, 2015, https://doi.org/10.3748/wjg.v21.i19.5843
  11. Reduced expression levels of let‑7c in human breast cancer patients 2015, https://doi.org/10.3892/ol.2015.2877
  12. Association of polymorphisms in long non-coding RNA H19 with coronary artery disease risk in a Chinese population vol.772, 2015, https://doi.org/10.1016/j.mrfmmm.2014.12.009
  13. Protective Effect of let-7 miRNA Family in Regulating Inflammation in Diabetes-Associated Atherosclerosis vol.66, pp.8, 2017, https://doi.org/10.2337/db16-1405
  14. Aberrant regulation of the LIN28A/LIN28B and let-7 loop in human malignant tumors and its effects on the hallmarks of cancer vol.14, pp.1, 2015, https://doi.org/10.1186/s12943-015-0402-5
  15. The Function and Therapeutic Potential of Long Non-coding RNAs in Cardiovascular Development and Disease vol.8, 2017, https://doi.org/10.1016/j.omtn.2017.07.014
  16. Structural insights into the transcription-independent apoptotic pathway of p53 vol.47, pp.3, 2014, https://doi.org/10.5483/BMBRep.2014.47.3.261
  17. Transcriptomic profiling of platelet senescence and platelet extracellular vesicles vol.57, pp.1, 2017, https://doi.org/10.1111/trf.13896
  18. Functional Roles of p38 Mitogen-Activated Protein Kinase in Macrophage-Mediated Inflammatory Responses vol.2014, 2014, https://doi.org/10.1155/2014/352371
  19. Let-7 in Cardiovascular Diseases, Heart Development and Cardiovascular Differentiation from Stem Cells vol.14, pp.11, 2013, https://doi.org/10.3390/ijms141123086
  20. Hepatic Extracellular Signal–Regulated Kinase 2 Suppresses Endoplasmic Reticulum Stress and Protects From Oxidative Stress and Endothelial Dysfunction vol.2, pp.4, 2013, https://doi.org/10.1161/JAHA.113.000361
  21. Let-7b binding site polymorphism in the B-cell lymphoma-extra large 3′UTR is associated with fluorouracil resistance of hepatocellular carcinoma vol.11, pp.1, 2014, https://doi.org/10.3892/mmr.2014.2692
  22. model of preconditioning vol.6, pp.1, 2017, https://doi.org/10.1080/20013078.2017.1390391
  23. Glomerulocapillary miRNA response to HLA-class I antibody in vitro and in vivo vol.7, pp.1, 2017, https://doi.org/10.1038/s41598-017-14674-5
  24. MiR-323b-5p acts as a novel diagnostic biomarker for critical limb ischemia in type 2 diabetic patients vol.8, pp.1, 2018, https://doi.org/10.1038/s41598-018-33310-4
  25. MicroRNA Let-7f-5p Promotes Bone Marrow Mesenchymal Stem Cells Survival by Targeting Caspase-3 in Alzheimer Disease Model vol.12, pp.1662-453X, 2018, https://doi.org/10.3389/fnins.2018.00333