MicroRNA-208a-3p contributes to connexin40 remolding in human chronic atrial fibrillation.
MicroRNA-208a-3p contributes to connexin40 remolding in human chronic atrial fibrillation.
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DOI：
10.3892/etm.2017.5225
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发表时间：
2017-12
影响因子：
2.7
通讯作者：
Zhong G
中科院分区：
文献类型：
--
作者：
Li S;Jiang Z;Wen L;Feng G;Zhong G
以往的研究表明，连接蛋白40（Cx40）重塑参与了心房颤动（AF）的发生。初步生物信息学分析表明，编码Cx40的GJA 5是microRNA-208 a-3 p（miR-208 a-3 p）的潜在靶mRNA。然而，miR-208 a-3 p对人类慢性AF中Cx40的确切作用仍然难以捉摸。本研究证实了miR-208 a-3 p在人类慢性AF中的作用，并进一步研究了miR-208 a-3 p对Cx40表达的影响。共入组19例AF患者和18例窦性心律（SR）患者。用miR-208 a-3 p抑制剂或模拟物处理AC 16细胞系。采用原位杂交和逆转录定量聚合酶链反应（RT-qPCR）检测患者右心耳（RAA）组织中miR-208 a-3 p的表达。此外，通过RT-qPCR和western blot分析检测患者RAA和经miR-208 a-3 p抑制剂或模拟物处理的AC 16细胞中Cx40的表达。进行荧光素酶测定以确认Cx40是否被miR-208 a-3 p直接靶向。与SR患者相比，AF患者中miR-208 a-3 p水平显著升高。相反，AF患者中Cx40蛋白水平显著降低，并且观察到Cx40的偏侧化。miR-208 a-3 p抑制剂导致AC 16细胞中Cx40蛋白表达显著上调，而miR-208 a-3 p模拟物导致显著下调。然而，荧光素酶检测表明GJA 5不是miR-208 a-3 p的直接靶基因。这些发现仍然表明miR-208 a-3 p可能通过介导心房Cx40重塑而参与人类慢性AF，并且可能代表AF的潜在治疗靶点。
Previous studies have demonstrated that connexin40 (Cx40) remolding is involved in atrial fibrillation (AF). GJA5 encoding Cx40 is a potential target mRNA of microRNA-208a-3p (miR-208a-3p), as indicated by preliminary bioinformatics analyses. However, the exact effect of miR-208a-3p on Cx40 in human chronic AF has remained elusive. The present study demonstrated the role of miR-208a-3p in human chronic AF and further investigated the effect of miR-208a-3p on Cx40 expression. A total of 19 patients with AF and 18 patients with sinus rhythm (SR) were enrolled. The AC16 cell line was treated with miR-208a-3p inhibitor or mimics. The miR-208a-3p in right atrial appendage (RAA) tissues of patients was measured by in situ hybridization and reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, the expression of Cx40 in the RAA of patients and in AC16 cells treated with miR-208a-3p inhibitor or mimics were detected by RT-qPCR and western blot analysis. A luciferase assay was performed to confirm whether Cx40 was directly targeted by miR-208a-3p. The miR-208a-3p levels in patients with AF were significantly increased compared with those in patients with SR. Conversely, the Cx40 protein levels were significantly decreased and lateralization of Cx40 was observed in patients with AF. miR-208a-3p inhibitor led to a significant upregulation of the protein expression of Cx40 in AC16 cells, while miR-208a-3p mimics led to a significant downregulation. However, the luciferase assay demonstrated that GJA5 was not a direct target gene of miR-208a-3p. The findings still suggested that miR-208a-3p may be involved in human chronic AF by mediating atrial Cx40 remolding, and may represent a potential therapeutic target for AF.
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