Wisp2 super-enhancer-associated RNA (WISPER) (WISPER)

Wisp2 super-enhancer-associated RNA (WISPER) is a cardiac fibroblast-enriched long non-coding RNA (lncRNA) that acts as a master regulator of cardiac fibrosis (Micheletti et al., 2017, Nature Communications). It is specifically expressed in cardiac fibroblasts and is significantly upregulated in the heart following myocardial infarction, where it correlates with the severity of fibrosis in human patients (Micheletti et al., 2017). Mechanistically, WISPER interacts with the RNA-binding protein TIA1 (T-cell intracellular antigen 1-related protein) to control the expression of a core program of genes essential for fibroblast proliferation, migration, and extracellular matrix deposition (Gomes et al., 2020, Cardiovascular Research). Experimental targeting of WISPER using antisense oligonucleotides (GapmeRs) has demonstrated the ability to reduce fibroblast activation and preserve cardiac function in vivo, making it a potent therapeutic candidate for treating heart failure (Micheletti et al., 2017). Its high tissue and cell-type specificity suggests that targeting WISPER could minimize systemic side effects compared to broader anti-fibrotic therapies.

Other names

Wisper long non-coding RNAWisp2 super-enhancer-associated RNAWISPER lncRNA

Antisense-mediated knockdown of WISPER lncRNA to inhibit the activation of cardiac fibroblasts and reduce the expression of pro-fibrotic genes.