Long noncoding RNA NRAV can regulate interferon-stimulated gene expression in melanoma
The long non-coding RNA Negative Regulator of Antiviral Response (NRAV) is known to suppress antiviral immunity by regulating interferon response, but its functional role in tumor immunology remains poorly understood. We examined the relevance of NRAV in melanoma and found that high NRAV expression was associated with poor survival, reduced inflammatory pathway activation, and resistance to…
A recently discovered long non-coding RNA named Negative Regulator of Antiviral Response (NRAV) appears to play a key role in suppressing antiviral immunity within melanoma cells. Research indicates that high levels of NRAV expression are linked to poor survival, reduced inflammatory pathway activation, and resistance to immune checkpoint blockade treatments.
Analysis of both bulk and single-cell transcriptomic data suggests that NRAV is expressed specifically in malignant cells, hinting at a cancer cell-specific function. By manipulating NRAV levels in the BRAF-mutant A375 melanoma model, researchers observed that stable NRAV overexpression dampens the activation of key interferon-stimulated genes (ISGs) following type-I and type-II interferon stimulation.
Conversely, NRAV knockdown trigger a corresponding increase in ISG transcription. Subcellular fractionation experiments revealed that NRAV primarily resides in the nuclear compartment of melanoma cells. Furthermore, alterations in regulatory histone marks on the target ISG promoters, particularly MX1 and IFITM3, were noted when NRAV expression was increased.
These findings collectively position NRAV as a tumor-intrinsic epigenetic regulator of interferon signaling, potentially contributing to melanoma's ability to evade the immune system.
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