The long non-coding RNA HLNC1 potentiates hepatocellular carcinoma progression via interaction with USP49

Abstract

Background: The hepatocellular carcinoma (HCC) represents a serious malignancy worldwide especially in China. Our transcriptome analysis identifies a novel long non-coding RNA (lncRNA) termed HLNC1. However, the function of HLNC1 in HCC remains to be determined. Methods: Novel lncRNAs were screened using lncRNA profiling. Relative expression was quantified by qRT-PCR. In vitro experiments such as migration and viability assays were performed. In vivo implantation experiments were conducted to investigate tumorigenic functions. RNA-RNA interaction assay was performed to determine USP49 as HLNC1 binding partner. Results: We found that HLNC1 was markedly upregulated in HCC samples and cell lines. HLNC1 could promote viability and migration of HCC cells. Meanwhile, we could also observe an oncogenic effect of HLNC1 in vivo. By RNA-RNA interaction assay, we unraveled USP49 transcript as the HLNC1 binding partner. HLNC1-USP49 interaction dramatically destabilized USP49. Heat-shock factor 1 (HSF1) was shown to directly induce HLNC1 expression. The therapeutic potential of targeting HLNC1 was investigated using antisense oligonucleotides (ASOs). The ASO construct which significantly depleted HLNC1 expression could strongly attenuate xenograft tumor growth. Conclusions: Our data suggested that HLNC1 may advance HCC progression and act as a potential target for intervention.