Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, People's Republic of China.
Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, No. 250 Changgang Dong Road, Guangzhou, 510260, Guangdong, People's Republic of China.
BMC Mol Biol. 2019 Mar 18;20(1):8. doi: 10.1186/s12867-019-0125-z.
Myocyte enhancer factor 2A (MEF2A) plays an important role in cell proliferation, differentiation and survival. Functional deletion or mutation in MEF2A predisposes individuals to cardiovascular disease mainly caused by vascular endothelial dysfunction. However, the effect of the inhibition of MEF2A expression on human coronary artery endothelial cells (HCAECs) is unclear. In this study, expression of MEF2A was inhibited by specific small interference RNA (siRNA), and changes in mRNA profiles in response to MEF2A knockdown were analyzed using an Agilent human mRNA array.
Silencing of MEF2A in HCAECs accelerated cell senescence and suppressed cell proliferation. Microarray analysis identified 962 differentially expressed genes (DEGs) between the MEF2A knockdown group and the negative control group. Annotation clustering analysis showed that the DEGs were preferentially enriched in gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to proliferation, development, survival, and inflammation. Furthermore, 61 of the 578 downregulated DEGs have at least one potential MEF2A binding site in the proximal promoter and were mostly enriched in the GO terms "reproduction" and "cardiovascular." The protein-protein interaction network analyzed for the downregulated DEGs and the DEGs in the GO terms "cardiovascular" and "aging" revealed that PIK3CG, IL1B, IL8, and PRKCB were included in hot nodes, and the regulation of the longevity-associated gene PIK3CG by MEF2A has been verified at the protein level, suggesting that PIK3CG might play a key role in MEF2A knockdown induced HCAEC senescence.
MEF2A knockdown accelerates HCAEC senescence, and the underlying molecular mechanism may be involved in down-regulation of the genes related with cell proliferation, development, inflammation and survival, in which PIK3CG may play a key role.
肌细胞增强因子 2A（MEF2A）在细胞增殖、分化和存活中发挥重要作用。MEF2A 的功能缺失或突变使个体易患主要由血管内皮功能障碍引起的心血管疾病。然而，抑制 MEF2A 表达对人冠状动脉内皮细胞（HCAEC）的影响尚不清楚。在这项研究中，通过特异性小干扰 RNA（siRNA）抑制 MEF2A 的表达，并用安捷伦人类 mRNA 芯片分析 MEF2A 敲低后 mRNA 谱的变化。
在 HCAEC 中沉默 MEF2A 可加速细胞衰老并抑制细胞增殖。微阵列分析确定了 MEF2A 敲低组和阴性对照组之间差异表达的基因（DEGs）有 962 个。注释聚类分析显示，DEGs 优先富集于与增殖、发育、存活和炎症相关的基因本体论（GO）术语和京都基因与基因组百科全书（KEGG）通路。此外，578 个下调 DEGs 中有 61 个在近端启动子中至少有一个潜在的 MEF2A 结合位点，且大多数富集于“繁殖”和“心血管”的 GO 术语中。下调 DEGs 和 GO 术语“心血管”和“衰老”中的 DEGs 的蛋白质-蛋白质相互作用网络分析表明，PIK3CG、IL1B、IL8 和 PRKCB 包含在热点节点中，MEF2A 对长寿相关基因 PIK3CG 的调控已在蛋白质水平得到验证，表明 PIK3CG 可能在 MEF2A 敲低诱导的 HCAEC 衰老中发挥关键作用。
MEF2A 敲低加速 HCAEC 衰老，其潜在的分子机制可能涉及与细胞增殖、发育、炎症和存活相关的基因下调，其中 PIK3CG 可能发挥关键作用。
