SP1-induced SNHG14 aggravates hypertrophic response in in vitro model of cardiac hypertrophy via up-regulation of PCDH17

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.