SPRY4-AS1, A Novel Enhancer RNA, Is a Potential Novel Prognostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma

A growing number of evidence have demonstrated the involvement of enhancer RNAs (eRNAs) in tumor progression. However, the possible functions of eRNAs in hepatocellular carcinoma (HCC) remain largely unclear. Our present research aimed to screen critical eRNAs and to further delve into the clinical significance of eRNAs in HCC patients. In this study, we identified 124 prognosis-related eRNAs by analyzing The Cancer Genome Atlas (TCGA) datasets. Among them, SPRY4 antisense RNA 1 (SPRY4-AS1) may be a key eRNA involved in HCC progression. SPRY4 was a regulatory target of SPRY4-AS1. High SPRY4-AS1 expression was associated with poor prognosis of HCC patients. Kyoto Encyclopedia of Genes and Genomes (KEGG) assays revealed that the mainly enriched biological process included Human papillomavirus infection, Hippo signaling pathway, and Proteoglycans in cancer. Besides, RT-PCR and immunohistochemical staining confirmed SPRY4-AS1 as an overexpressed eRNA in HCC specimens. The pan-cancer assays revealed that SPRY4-AS1 was associated with glioblastoma multiforme (GBM), adrenocortical carcinoma (ACC), brain lower grade glioma (LGG) and mesothelioma(MESO). Positive associations were observed between SPRY4-AS1 and SPRY4 (its target gene) in 16 tumor types. Collectively, our findings reveal a novel eRNA SPRY4-AS1 for HCC progression and suggest that SPRY4-AS1 may be a potential biomarker and therapeutic target for HCC.