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MicroRNA-29a-3p regulates abdominal aortic aneurysm development and progression via direct interaction with PTEN.
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-05-07 , DOI: 10.1002/jcp.29746
Yuan Zhou 1 , Meigui Wang 1 , Jing Zhang 2 , Peng Xu 1 , Haitao Wang 2
Affiliation  

Various research studies have been conducted in deducing the role of microRNAs (miRNAs) in the pathogenesis and physiological processes of various systematic diseases. This study aims at demonstration of the important role played by miR‐29a‐3p, through association with phosphatase and tensin homolog (PTEN), in the regulation of abdominal aortic aneurysm development and progression. Quantitative real‐time polymerase chain reaction (RT‐qPCR) examined miRNA‐19a‐3p and PMEPA1 expression in multiplied vascular smooth muscle cells (VSMCs). Cell transfection upregulated or downregulated the genes and cell counting kit‐8 assay determined cellular viability. RT‐qPCR detected cellular proliferation and cell death using the cell proliferation and apoptosis biomarkers Ki87 and proliferating cell nuclear antigen, caspase‐8 and caspase‐3, respectively. Furthermore, luciferase assay analyzed the luciferase activity and western blot analysis determined miRNA‐19a‐3p and PMEPA1 protein expression in proliferation and apoptosis biomarkers. TargetScan 4.2 online software (www.targetscan.org) was used to perform the bioinformatics analysis so as to forecast the putative targets of miR‐29a‐3p and PTEN. The results inferred that there was an increased expression of miRNA‐29a‐3p found in AAA‐mimic cells with increased cellular viability and significant pathological apoptosis. Further, when the expression of miRNA‐29a‐3p was downregulated, it reduced the cell viability of AAA cells. On the basis of the gene interplays, it can be understood that the PTEN was directly targeted by miRNA‐29a‐3p so as to regulate the AAA progression. Thus, PTEN was found to strengthen the proliferation effect of miRNA‐29a‐3p in AAA cells. The current study thus shed more insights about the molecular mechanistic roles of miRNA‐29a‐3p and PTEN, opening doors for novel therapeutic approach to AAA.

中文翻译:

MicroRNA-29a-3p通过与PTEN直接相互作用来调节腹主动脉瘤的发生和发展。

在推断微小RNA(miRNA)在各种系统疾病的发病机理和生理过程中的作用方面已经进行了各种研究。这项研究旨在证明miR‐29a‐3p通过与磷酸酶和张力蛋白同源物(PTEN)结合在调节腹主动脉瘤的发生和发展中发挥重要作用。实时定量聚合酶链反应(RT-qPCR)检测了倍增的血管平滑肌细胞(VSMC)中的miRNA-19a-3p和PMEPA1表达。细胞转染上调或下调基因,细胞计数试剂盒8测定确定细胞活力。RT-qPCR使用细胞增殖和凋亡生物标记物Ki87和增殖细胞核抗原caspase-8和caspase-3分别检测细胞增殖和细胞死亡。此外,萤光素酶测定分析了萤光素酶活性,蛋白质印迹分析确定了增殖和凋亡生物标志物中的miRNA-19a-3p和PMEPA1蛋白表达。使用TargetScan 4.2在线软件(www.targetscan.org)进行生物信息学分析,以预测miR‐29a‐3p和PTEN的假定靶标。结果表明,在AAA模拟细胞中发现的miRNA‐29a‐3p表达增加,具有较高的细胞活力和明显的病理细胞凋亡。此外,当miRNA‐29a‐3p的表达下调时,它会降低AAA细胞的细胞活力。根据基因相互作用,可以理解,miRNA-29a-3p直接靶向PTEN,以调节AAA进程。从而,发现PTEN可以增强miRNA‐29a‐3p在AAA细胞中的增殖作用。因此,本研究对miRNA‐29a‐3p和PTEN的分子机制作用有了更多的了解,为AAA的新型治疗方法打开了大门。
更新日期:2020-05-07
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