Upregulation of lncRNA VDR/CASC15 induced by facilitates cardiac hypertrophy through modulating miR-432-5p/TLR4 axis.

Sustained cardiac hypertrophy has threatened human health. With the development of human genome project, non-coding RNAs (ncRNAs) have attracted more and more attentions of researchers. As a subgroup of ncRNAs, long non-coding RNAs (lncRNAs) has been widely studied in human diseases, including cardiac hypertrophy. According to search results of bioinformatics website, lncRNA CASC15 potentially participates in the course of cardiac hypertrophy. According to the result of qRT-PCR, CASC15 expression was upregulated when cardiomyocytes were treated with Ang-II. Moreover, CASC15 was highly expressed in cardiac hypertrophic model. Upregulation of CASC15 was accompanied with some hypertrophic responses. To explore the specific biological function of CASC15 in cardiac hypertrophy, loss-of-function experiments were conducted in Ang-II-induced cardiomyocytes. Results of immunofluorence staining revealed that cell surface area enlarged by Ang-II was decreased when CASC15 was silenced. The expression levels of hypertrophic factors were attenuated by knockdown of CASC15. To detect the molecular mechanism by which CASC15 regulates the progression of cardiac hypertrophy, mechanism experiments were designed and carried out. It was found that CASC15 was activated by the transcription factor VDR. Furthermore, CASC15 can upregulate TLR4 by competitively binding miR-432-5p. In conclusion, Upregulation of lncRNA CASC15 induced by VDR facilitates cardiac hypertrophy via miR-432-5p/TLR4 axis.