Identifying Long Non-Coding RNAs Associated with a Protective Type I Interferon Signature in Melanoma

Abstract

Long non-coding RNAs (lncRNAs) have emerged as a new class of regulators of type I interferon (IFN) signaling and can potentially serve as therapeutic targets.1 In this study, we identified lncRNAs that are associated with both a strong type I IFN response, characterized by increased interferon-stimulated gene (ISG) expression, and high survival rate in cancer patients. In particular, we are interested in the effect of lncRNA-induced differential ISG expression in the context of melanoma. To study the effects of lncRNA on ISG expression, we performed gain-of-function experiments in two systems – A375 melanoma cell line and melanoma short-term culture (MSTC). We used Lipofectamine to transfect plasmids containing lncRNA of interest into these systems, and then performed RT-qPCR to assess ISG expression. We used the term “ISG signature” to refer to the unique gene expression differences observed upon lncRNA overexpression in our experimental set up. Here, we identified one lncRNA, HCP5-204, to be significantly associated with a protective ISG signature in melanoma, consisting of ISG15, STAT1, IRF9, JAK1, and TLR3. Future experiments will explore the mechanisms of action through which HCP5-204 modulates type I IFN response in melanoma.