Long noncoding RNA glypican 3 (GPC3) antisense transcript 1 promotes hepatocellular carcinoma progression via epigenetically activating GPC3

Abstract

Long noncoding RNA (lnc RNA) have critical roles in various pathophysiological processes, and are frequently dysregulated in many diseases, particularly in cancer. The lnc RNA glypican 3 antisense transcript 1 (GPC3‐AS 1) has been reported to be a potential biomarker for hepatocellular carcinoma (HCC) screening. However, the exact biological functions of GPC 3‐AS 1 in HCC, and its roles and regulation mechanisms regarding GPC 3 are still unknown. In this study, we observed a significant upregulation of GPC 3‐AS 1 in HCC. Increased expression of GPC 3‐AS 1 was associated with α‐fetoprotein, tumor size, microvascular invasion, encapsulation, Barcelona Clinic Liver Cancer stage, and worse prognosis of HCC patients. Furthermore, we found that GPC 3‐AS 1 physically associated with P300/CBP‐associated factor and recruited it to the GPC 3 gene body region, consequently inducing an increase in euchromatic histone marks and activating GPC 3 transcription. GPC 3‐AS 1 expression was strongly correlated with GPC 3 in HCC tissues. Gain‐of‐function and loss‐of‐function analyses showed that GPC 3‐AS 1 overexpression enhanced HCC cell proliferation and migration in vitro and xenograft tumor growth in vivo. GPC 3‐AS 1 knockdown inhibited HCC cell proliferation and migration. Moreover, the effects of GPC 3‐AS 1 on HCC cell proliferation and migration were dependent on the upregulation of GPC 3. Collectively, our studies indicate that GPC 3‐AS 1 significantly promotes HCC progression via epigenetically activating GPC 3, and identifies GPC 3‐AS 1 as a potential therapeutic target for HCC.