The lncRNA Plscr4 Controls Cardiac Hypertrophy by Regulating miR-214

Abstract

Cardiac hypertrophy accompanied by maladaptive cardiac remodeling is the uppermost risk factor for the development of heart failure. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have various biological functions, and their vital role in the regulation of cardiac hypertrophy still needs to be explored. In this study, we demonstrated that lncRNA Plscr4 was upregulated in hypertrophic mice hearts and in angiotensin II (Ang II)–treated cardiomyocytes. Next, we observed that overexpression of Plscr4 attenuated Ang II-induced cardiomyocyte hypertrophy. Conversely, the inhibition of Plscr4 gave rise to cardiomyocyte hypertrophy. Furthermore, overexpression of Plscr4 attenuated TAC (transverse aortic constriction)-induced cardiac hypertrophy. Finally, we demonstrated that Plscr4 acted as an endogenous sponge of miR-214 and forced expression of Plscr4 downregulated miR-214 expression to promote Mfn2 and attenuate hypertrophy. In contrast, knockdown of Plscr4 upregulated miR-214 to induce cardiomyocyte hypertrophy. Additionally, luciferase assay showed that miR-214 was the direct target of Plscr4, and overexpression of miR-214 counteracted the anti-hypertrophy effect of Plscr4. Collectively, these findings identify Plscr4 as a negative regulator of cardiac hypertrophy in vivo and in vitro due to its regulation of the miR-214-Mfn2 axis, suggesting that Plscr4 might act as a therapeutic target for the treatment of cardiac hypertrophy and heart failure.

Identification of functional lncRNAs in atrial fibrillation by integrative analysis of the lncRNA‐mRNA network based on competing endogenous RNAs hypothesis

“…Interestingly, this regulatory mechanism has been observed in some cardiovascular diseases. For example, lncRNA Plscr4 was shown to function as a ceRNA to upregulate Mfn2 and attenuate hypertrophy by modulating miR‐214 (Lv et al, ). In addition, lncRNA MALAT1 could promote myocardial fibrosis and deteriorate cardiac function by serving as a ceRNA for miR‐145 to affect transforming growth factor beta 1 (TGF‐β1) activity (S. Huang et al, ).…”

Long non‐coding RNA small nucleolar RNA host gene 7 facilitates cardiac hypertrophy via stabilization of SDA1 domain containing 1 mRNA

“…lncRNAs are known to be a cluster of transcripts possessing little or no protein coding potential . Increasing research works have demonstrated the significant involvement of lncRNAs in human cancers and diseases, including in cardiac hypertrophy . SNHG7 is identified to bear oncogenic potential in multiple cancers .…”

LncRNAs in cardiac hypertrophy: From basic science to clinical application

“…With more and more genetic anal- giotensin II (Ang-II). 33,56,58 Overexpression of Lnc-H19, Lnc-SNHG1, Lnc-uc.323 or loss-expression of Lnc-Ahit and Lnc-Chast could reduce the cardiomyocytes size in response to phenylephrine. 36,47,59,60 Conditional knockout of Lnc-DACH or overexpression Lnc-TINCR resulted in increasing calcium transient, and improving cardiac function after transverse aortic constriction in mice.…”