Several studies have indicated that long noncoding RNAs (lncRNAs)-HOX transcript antisense RNA (HOTAIR) is involved in some cardiovascular diseases by regulating gene expression as a competitive endogenous RNA (ceRNA). GJA1 encoding Cx43 is one potential target gene of microRNA-613 (miR-613). Meanwhile, there is a potential target regulatory relationship between HOTAIR and miR-613. The present study is aimed at investigating whether HOTAIR functions as a ceRNA to regulate the Cx43 expression in atrial fibrillation (AF) by sponging miR-613. The expressions of HOTAIR, miR-613, and Cx43 were detected in the right atrial appendages of 45 patients with heart valve disease, including 23 patients with chronic AF. The HOTAIR overexpressed and underexpressed HL-1 cell model were constructed to confirm the effect of HOTAIR on Cx43. Then, the Cx43 expression was detected to testify the interplay between HOTAIR and miR-613 after cotransfecting HOTAIR and miR-613. Furthermore, luciferase assays were performed to verify that HOTAIR could regulate Cx43 remolding as a ceRNA by sponging miR-613. The expression of HOTAIR and Cx43 was significantly downregulated in chronic AF group. HOTAIR regulated positively the Cx43 expression in HL-1 cells. The upregulated effect of HOTAIR on the Cx43 expression could be remarkably attenuated by miR-613. Moreover, the inhibitory effect of miR-613 on the Cx43 expression could be obviously mitigated by HOTAIR. At last, luciferase assays confirmed HOTAIR functioned as a ceRNA in the Cx43 expression by sponging miR-613. Our study suggests that HOTAIR, functioning as a ceRNA by sponging miR-613, is an important contributor to Cx43 remolding in AF.

中文翻译：

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长非编码RNA HOTAIR充当竞争性内源RNA，通过海绵MicroRNA-613调节房颤的Connexin43重塑。

多项研究表明，长时非编码RNA（lncRNA）-HOX转录反义RNA（HOTAIR）通过调节作为竞争性内源RNA（ceRNA）的基因表达而参与某些心血管疾病。编码Cx43的GJA1是microRNA-613（miR-613）的一种潜在靶基因。同时，HOTAIR和miR-613之间存在潜在的目标调控关系。本研究旨在研究HOTAIR是否通过使miR-613变海绵来充当ceRNA来调节房颤（AF）中Cx43表达。在45例心脏瓣膜病患者，包括23例慢性AF患者的右心耳中检测到HOTAIR，miR-613和Cx43的表达。构建了HOTAIR高表达和低表达的HL-1细胞模型，以确认HOTAIR对Cx43的作用。然后，共转染HOTAIR和miR-613后，检测到Cx43表达以证明HOTAIR和miR-613之间的相互作用。此外，进行了荧光素酶测定以验证HOTAIR可以通过海绵化miR-613来调控Cx43重塑为ceRNA。慢性AF组HOTAIR和Cx43的表达明显下调。HOTAIR积极调节HL-1细胞中Cx43的表达。miR-613可以显着减弱HOTAIR对Cx43表达的上调作用。而且，HOTAIR可以明显减轻miR-613对Cx43表达的抑制作用。最后，萤光素酶测定证实，通过使miR-613变海绵，HOTAIR在Cx43表达中起ceRNA的作用。我们的研究表明，HOTAIR通过海绵化miR-613发挥ceRNA的作用，是AF中Cx43重塑的重要贡献者。