Investigating the Role of the Post-transcriptional Gene Regulator MiR-24-3p in the Proliferation, Migration and Apoptosis of Human Arterial Smooth Muscle Cells in Arteriosclerosis Obliterans
Investigating the Role of the Post-transcriptional Gene Regulator MiR-24-3p in the Proliferation, Migration and Apoptosis of Human Arterial Smooth Muscle Cells in Arteriosclerosis Obliterans
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研究转录后基因调节因子 MiR-24-3p 在动脉硬化闭塞症中人动脉平滑肌细胞增殖、迁移和凋亡中的作用
DOI：
10.1159/000430302
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发表时间：
2015-07
影响因子：
--
通讯作者：
Wang, Shen-ming
中科院分区：
文献类型：
--
作者：
Wu, Wei-bin;Shi, Ya-wei;Li, Wen;Wang, Shen-ming
目的：探讨miR-24-3p在动脉硬化闭塞症(ASO)患者动脉中的表达及其在ASO发病机制中的作用。方法：采用实时定量聚合酶链式反应(qRT-PCR)和原位杂交技术检测人动脉miR-24-3p的表达。为了研究miR-24-3p对人动脉平滑肌细胞(HASMCs)的影响，我们应用细胞计数和EDU法检测细胞增殖，用跨膜和伤口愈合实验检测细胞迁移，用流式细胞术检测细胞凋亡。此外，我们还应用3‘-非翻译区(3’-UTR)荧光素酶分析来研究miR-24-3p在靶向血小板衍生生长因子受体B(PDGFRb)和c-Myc中的作用。结果：与正常动脉相比，MIR-24-3p主要定位于动脉中层，ASO动脉MIR-24-3p表达下调。血小板衍生生长因子BB(PDGF-BB)可降低原代培养的HASMCs miR-24-3p的表达。MIR-24-3P模拟寡核苷酸抑制HASMCs的增殖和迁移，促进细胞凋亡。我们的3‘-UTR荧光素酶分析证实PDGFRb和c-Myc是miR-24-3p的靶标。结论：miR-24-3p通过靶向PDGFRb和c-Myc调控HASMCs的增殖和迁移。PDGF/miR-24-3p/PDGFRb和PDGF/miR-24-3p/c-Myc通路可能在ASO的发病机制中起重要作用。这些发现突出了ASO新的治疗靶点的潜力。
Aims: To explore the expression of miR-24-3p in human arteries with arteriosclerosis obliterans (ASO) as well as the role of miR-24-3p in the pathogenesis of ASO. Methods: We used quantitative real-time PCR (qRT-PCR) and in situ hybridization to monitor miR-24-3p expression in human arteries. To investigate the effect of miR-24-3p on human arterial smooth muscle cells (HASMCs), we applied cell counting and EdU assays to monitor proliferation and transwell and wound healing assays to investigate migration and flow cytometry to investigate apoptosis. Furthermore, we applied 3'-untranslated region (3'-UTR) luciferase assays to investigate the role of miR-24-3p in targeting platelet-derived growth factor receptor B (PDGFRB) and c-Myc. Results: MiR-24-3p was mainly located in the media of arteries and was downregulated in ASO arteries compared with normal arteries. Platelet-derived growth factor BB (PDGF-BB) treatment reduced the expression of miR-24-3p in primary cultured HASMCs. MiR-24-3p mimic oligos inhibited the proliferation and migration, and promotes apoptosis of HASMCs. Our 3'-UTR luciferase assays confirmed that PDGFRB and c-Myc were targets of miR-24-3p. Conclusion: The results suggest that miR-24-3p regulates the proliferation and migration of HASMCs by targeting PDGFRB and c-Myc. The PDGF/miR-24-3p/PDGFRB and PDGF/miR-24-3p/c-Myc pathways may play critical roles in the pathogenesis of ASO. These findings highlight the potential for new therapeutic targets for ASO.
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影响因子：
5.8
作者：
Madrigal-Matute, Julio;Rotllan, Noemi;Aranda, Juan F.;Fernandez-Hernando, Carlos
通讯作者：
Fernandez-Hernando, Carlos
影响因子：
120.7
作者：
Fowkes, F. G. R.;Murray, G. D.;Butcher, I.;Heald, C. L.;Lee, R. J.;Chambless, L. E.;Folsom, A. R.;Hirsch, A. T.;Dramaix, M.;deBacker, G.;Wautrecht, J-C.;Kornitzer, M.;Newman, A. B.;Cushman, M.;Sutton-Tyrrell, K.;Lee, A. J.;Price, J. F.;d'Agostino, R. B.;Murabito, J. M.;Norman, P. E.;Jamrozik, K.;Curb, J. D.;Masaki, K. H.;Rodriquez, B. L.;Dekker, J. M.;Bouter, L. M.;Heine, R. J.;Nijpels, G.;Stehouwer, C. D. A.;Ferrucci, L.;McDermott, M. M.;Stoffers, H. E.;Hooi, J. D.;Knottnerus, J. A.;Ogren, M.;Hedblad, B.;Witteman, J. C.;Breteler, M. M. B.;Hunink, M. G. M.;Hofman, A.;Criqui, M. H.;Langer, R. D.;Fronek, A.;Hiatt, W. R.;Hamman, R.;Resnick, H. E.;Guralnik, J.;McDermott, M. M.
通讯作者：
McDermott, M. M.
DOI：
10.1161/atvbaha.114.304088
发表时间：
2014-09-01
影响因子：
8.7
作者：
Di Gregoli, Karina;Jenkins, Nicholas;Johnson, Jason L.
通讯作者：
Johnson, Jason L.
DOI：
10.3410/f.1383966.856065
发表时间：
2010-01
期刊：
--
影响因子：
--
作者：
K. Gross
通讯作者：
K. Gross
影响因子：
168.9
作者：
Lozano, Rafael;Naghavi, Mohsen;Murray, Christopher J. L.
通讯作者：
Murray, Christopher J. L.