title: Long noncoding RNA glypican 3 (GPC3) antisense transcript 1 promotes hepatocellular carcinoma progression via epigenetically activating GPC3.
abstract: Long noncoding RNA (lncRNA) have critical roles in various pathophysiological processes, and are frequently dysregulated in many diseases, particularly in cancer. The lncRNA glypican 3 antisense transcript 1 (GPC3-AS1) has been reported to be a potential biomarker for hepatocellular carcinoma (HCC) screening. However, the exact biological functions of GPC3-AS1 in HCC, and its roles and regulation mechanisms regarding GPC3 are still unknown. In this study, we observed a significant upregulation of GPC3-AS1 in HCC. Increased expression of GPC3-AS1 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 GPC3-AS1 physically associated with P300/CBP-associated factor and recruited it to the GPC3 gene body region, consequently inducing an increase in euchromatic histone marks and activating GPC3 transcription. GPC3-AS1 expression was strongly correlated with GPC3 in HCC tissues. Gain-of-function and loss-of-function analyses showed that GPC3-AS1 overexpression enhanced HCC cell proliferation and migration in vitro and xenograft tumor growth in vivo. GPC3-AS1 knockdown inhibited HCC cell proliferation and migration. Moreover, the effects of GPC3-AS1 on HCC cell proliferation and migration were dependent on the upregulation of GPC3. Collectively, our studies indicate that GPC3-AS1 significantly promotes HCC progression via epigenetically activating GPC3, and identifies GPC3-AS1 as a potential therapeutic target for HCC.
authors: Department of Anatomy, Histology and Embryology, Shanghai Jiao Tong University School of Medicine, China.
authors: Xiao-Ting
authors: XT
authors: Zhu
authors: Department of Medical Genetics, Second Military Medical University, Shanghai, China. jihangyuan@smmu.edu.cn.
authors: Ji-Hang
authors: JH
authors: Yuan
authors: Department of Anatomy, Histology and Embryology, Shanghai Jiao Tong University School of Medicine, China.
authors: Teng-Teng
authors: TT
authors: Zhu
authors: Department of Anatomy, Histology and Embryology, Shanghai Jiao Tong University School of Medicine, China.
authors: Yang-Yang
authors: YY
authors: Li
authors: Department of Anatomy, Histology and Embryology, Shanghai Jiao Tong University School of Medicine, China. xycheng@shsmu.edu.cn.
authors: Xiao-Yang
authors: XY
authors: Cheng
mesh_terms: D000107:Acetylation; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D044127:Epigenesis, Genetic; D053673:Glypicans / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D056945:Hep G2 Cells; D064593:Heterografts; D006657:Histones / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D015533:Transcriptional Activation; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: C097353:AFP protein, human; D014408:Biomarkers, Tumor; C105937:GPC3 protein, human; D053673:Glypicans; D006657:Histones; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D000509:alpha-Fetoproteins
keywords: GPC3; epigenetics; hepatocellular carcinoma; long noncoding RNA; progression