Cardiac hypertrophy (CH) is a common cardiac disease and is closely associated with heart failure. Protocadherin 17 (PCDH17) was reported to aggravate myocardial infarction. Present study was designed to illustrate the impact of PCDH17 and the mechanism of PCDH17 expression regulation in CH. CH model in vivo and in vitro was established by transverse aortic constriction (TAC) and Ang‐II treatment. Hypertrophy was evaluated in PMC and H9c2 cells by examining cell surface area and hypertrophic markers. Results demonstrated that PCDH17 was up‐regulated in CH in vivo and in vitro. PCDH17 knock‐down alleviated hypertrophic response in Ang‐II‐induced cardiomyocytes. By means of ENCORI database and a series of mechanism assays, miR‐322‐5p and miR‐384‐5p were identified to interact with and inhibit PCDH17. Next, lncRNA SNHG14 (small nucleolar RNA host gene 14) was validated to sponge both miR‐322‐5p and miR‐384‐5p to elevate PCDH17 level. The subsequent rescue assays revealed that miR‐322‐5p and miR‐384‐5p restored SNHG14 depletion‐mediated suppression on hypertrophy in Ang‐II‐induced cardiomyocytes. Besides, Sp1 transcription factor (SP1) was verified as the transcription factor activating both SNHG14 and PCDH17. Both SNHG14 and PCDH17 reversed SP1 knock‐down‐mediated repression on hypertrophy in Ang‐II‐induced cardiomyocytes. Together, present study first uncovered ceRNA network of SNHG14/miR‐322‐5p/miR‐384‐5p/PCDH17 in Ang‐II‐induced cardiomyocytes.

中文翻译：

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SP1诱导的SNHG14通过PCDH17的上调加重心肌肥大体外模型中的肥大反应。

心脏肥大（CH）是一种常见的心脏病，与心力衰竭密切相关。据报道原钙粘蛋白17（PCDH17）加重了心肌梗塞。本研究旨在说明PCDH17的影响以及PCDH17表达调节在CH中的作用。通过横向主动脉缩窄（TAC）和Ang-II治疗建立体内和体外CH模型。通过检查细胞表面积和肥大标志物评估PMC和H9c2细胞的肥大。结果表明，体内外的CH中PCDH17均被上调。PCDH17敲低减轻了Ang II诱导的心肌细胞的肥大反应。通过ENCORI数据库和一系列机理分析，鉴定出miR-322-5p和miR-384-5p与PCDH17相互作用并抑制PCDH17。下一个，lncRNA SNHG14（小核仁RNA宿主基因14）经过验证，可以使miR-322-5p和miR-384-5p都升高PCDH17水平。随后的急救分析显示，miR-322-5p和miR-384-5p恢复了AngII诱导的心肌细胞中SNHG14耗竭介导的肥大抑制。此外，Sp1转录因子（SP1）被证实是激活SNHG14和PCDH17的转录因子。SNHG14和PCDH17均可逆转AngII诱导的心肌细胞中SP1敲低介导的肥大抑制。总之，本研究首次在AngII诱导的心肌细胞中发现了SNHG14 / miR-322-5p / miR-384-5p / PCDH17的ceRNA网络。随后的急救分析显示，miR-322-5p和miR-384-5p恢复了AngII诱导的心肌细胞中SNHG14耗竭介导的肥大抑制。此外，Sp1转录因子（SP1）被证实是激活SNHG14和PCDH17的转录因子。SNHG14和PCDH17均可逆转AngII诱导的心肌细胞中SP1敲低介导的肥大抑制。总之，本研究首次在AngII诱导的心肌细胞中发现了SNHG14 / miR-322-5p / miR-384-5p / PCDH17的ceRNA网络。随后的急救分析表明，miR-322-5p和miR-384-5p恢复了SNHG14耗尽介导的Ang-II诱导的心肌肥大抑制作用。此外，Sp1转录因子（SP1）被证实是激活SNHG14和PCDH17的转录因子。SNHG14和PCDH17均可逆转AngII诱导的心肌细胞中SP1敲低介导的肥大抑制。总之，本研究首次在AngII诱导的心肌细胞中发现了SNHG14 / miR-322-5p / miR-384-5p / PCDH17的ceRNA网络。