{Reference Type}: Journal Article
{Title}: Super-enhancer-driven lncRNA Snhg7 aggravates cardiac hypertrophy via Tbx5/GLS2/ferroptosis axis.
{Author}: Zhang Q;Song C;Zhang M;Liu Y;Wang L;Xie Y;Qi H;Ba L;Shi P;Cao Y;Sun H;
{Journal}: Eur J Pharmacol
{Volume}: 953
{Issue}: 0
{Year}: 2023 Aug 15
{Factor}: 5.195
{DOI}: 10.1016/j.ejphar.2023.175822
{Abstract}: Long non-coding RNAs (lncRNAs) are expressed aberrantly in cardiac disease, but their roles in cardiac hypertrophy are still unknown. Here we sought to identify a specific lncRNA and explore the mechanisms underlying lncRNA functions. Our results revealed that lncRNA Snhg7 was a super-enhancer-driven gene in cardiac hypertrophy by using chromatin immunoprecipitation sequencing (ChIP-seq). We next found that lncRNA Snhg7 induced ferroptosis by interacting with T-box transcription factor 5 (Tbx5), a cardiac transcription factor. Moreover, Tbx5 bound to the promoter of glutaminase 2 (GLS2) and regulated cardiomyocyte ferroptosis activity in cardiac hypertrophy. Importantly, extra-terminal domain inhibitor JQ1 could suppress super-enhancers in cardiac hypertrophy. Inhibition of lncRNA Snhg7 could block the expressions of Tbx5, GLS2 and levels of ferroptosis in cardiomyocytes. Furthermore, we verified that Nkx2-5 as a core transcription factor, directly bound the super-enhancer of itself and lncRNA Snhg7, increasing both of their activation. Collectively, we are the first to identify lncRNA Snhg7 as a novel functional lncRNA in cardiac hypertrophy, might regulate cardiac hypertrophy via ferroptosis. Mechanistically, lncRNA Snhg7 could transcriptionally regulate Tbx5/GLS2/ferroptosis in cardiomyocytes.