High expression of IncRNA HSD11B1-AS1 indicates favorable prognosis and is associated with immune infiltration in cutaneous melanoma

摘要

Cutaneous melanoma is an aggressive malignant cancer associated with poor prognosis. Identification of reliable biomarkers for predicting prognosis of melanoma contributes to improved clinical outcome and disease management. Long non-coding RNAs (lncRNAs) serve a crucial regulatory role of oncogenesis and tumor suppression in melanoma. Using data from The Cancer Genome Atlas database, novel lncRNA 11p-hydroxysteroid dehydrogenase type 1-antisense RNA 1 (HSD11B1-AS1) was identified, which was significantly down-regulated in malignant melanoma and its downregulation was significantly associated with poor clinicopathological characteristics, including advanced T and pathological stage, Clark level, Breslow depth and ulceration and worse prognosis. Multivariate analysis showed that HSD11B1-AS1, as well as N stage and Breslow depth, were independent prognostic factors in cutaneous melanoma, and nomograms suggested a good predictive value of 1-, 3- and 5-year overall survival, progression-free interval and disease-specific survival. In vitro experiments verified the decreased HSD11B1-AS1 expression in melanoma cell lines compared with human epidermal melanocytes. Moreover, cell experiments in vitro,including Cell Counting Kit-8, colony formation, wound healing and Transwell assay, suggested that overexpression of HSD11B1-AS1 significantly inhibited melanoma cell proliferation, migration and invasion. Functional enrichment showed significantly enriched pathways in IFN-γ and -αresponse, TNF-α signaling via NF-kB and IL-2/STAT-5 and IL-6/JAK/STAT-3 signaling. In addition, immune infiltration analysis demonstrated that HSD11B1-AS1 may function by accelerating immune response regulation and the immune cell infiltration of various immunocytes, especially T, T helper 1, activated dendritic and B cells. The present study revealed HSD11B1-AS1 as a potential therapeutic target and promising biomarker for diagnosis and prognosis of cutaneous melanoma.