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靶向PIM-1的MiR-328抑制血小板衍生生长因子BB信号通路中肺动脉平滑肌细胞的增殖和迁移。

MiR-328 targeting PIM-1 inhibits proliferation and migration of pulmonary arterial smooth muscle cells in PDGFBB signaling pathway.

作者信息

Qian Zhengjiang, Zhang Limin, Chen Jidong, Li Yanjiao, Kang Kang, Qu Junle, Wang Zhiwei, Zhai Yujia, Li Li, Gou Deming

机构信息

Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong, 518060, China.

Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China.

出版信息

Oncotarget. 2016 Aug 23;7(34):54998-55011. doi: 10.18632/oncotarget.10714.

DOI:10.18632/oncotarget.10714
PMID:27448984
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5342397/
Abstract

MicroRNAs (miRNAs) have been recognized to mediate PDGF-induced cell dysregulation, but their exact functions remain to be elucidated. By using a sensitive S-Poly(T) Plus qRT-PCR method, the expression profiling of 1,078 miRNAs were investigated in pulmonary artery smooth muscle cells (PASMCs) with or without PDGFBB stimulation. MiR-328 was found as a prominent down-regulated miRNA, displaying a specific dose- and time-dependent downregulation upon PDGFBB exposure. Functional analyses revealed that miR-328 could inhibit PASMCs proliferation and migration both with and without PDGFBB treatment. The Ser/Thr-protein kinase-1 (PIM-1) was identified as a direct target of miR-328, and functionally confirmed by a rescue experiment. In addition, the decrease of miR-328 by PDGFBB might be due to the increased expression of DNA methylation transferase 1 (DNMT1) and DNA methylation. Finally, serum miR-328 level was downregulated in PAH patients associated with congenital heart disease (CHD- PAH). Overall, this study provides critical insight into fundamental regulatory mechanism of miR-328 in PDGFBB-activited PASMCs via targeting PIM- 1, and implies the potential of serum miR-328 level as a circulating biomarker for CHD- PAH diagnosis.

摘要

微小RNA(miRNA)已被认为可介导血小板衍生生长因子(PDGF)诱导的细胞失调,但其确切功能仍有待阐明。通过使用灵敏的S-Poly(T) Plus qRT-PCR方法,研究了1078种miRNA在有无PDGFBB刺激的肺动脉平滑肌细胞(PASMC)中的表达谱。发现miR-328是一种显著下调的miRNA,在暴露于PDGFBB时呈现出特定的剂量和时间依赖性下调。功能分析表明,无论有无PDGFBB处理,miR-328均可抑制PASMC的增殖和迁移。丝氨酸/苏氨酸蛋白激酶-1(PIM-1)被确定为miR-328的直接靶点,并通过挽救实验进行了功能验证。此外,PDGFBB导致的miR-328减少可能是由于DNA甲基转移酶1(DNMT1)表达增加和DNA甲基化所致。最后,先天性心脏病相关性肺动脉高压(CHD-PAH)患者血清miR-328水平下调。总体而言,本研究为miR-328通过靶向PIM-1在PDGFBB激活的PASMC中的基本调控机制提供了关键见解,并暗示血清miR-328水平作为CHD-PAH诊断的循环生物标志物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/ad3ab000149d/oncotarget-07-54998-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/b749d624c4da/oncotarget-07-54998-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/4a932046e567/oncotarget-07-54998-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/979143549f38/oncotarget-07-54998-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/c0e650551bb9/oncotarget-07-54998-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/70c538519439/oncotarget-07-54998-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/ff13c77bb9d6/oncotarget-07-54998-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/8cda8a971667/oncotarget-07-54998-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/ad3ab000149d/oncotarget-07-54998-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/b749d624c4da/oncotarget-07-54998-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/4a932046e567/oncotarget-07-54998-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/979143549f38/oncotarget-07-54998-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/c0e650551bb9/oncotarget-07-54998-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/70c538519439/oncotarget-07-54998-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/ff13c77bb9d6/oncotarget-07-54998-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/8cda8a971667/oncotarget-07-54998-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/5342397/ad3ab000149d/oncotarget-07-54998-g008.jpg

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