Abstract
Objective: Increasing evidence highlights antisense long non-coding RNAs (lncRNAs) as promising therapeutic targets for cancers. Herein, this study focused on the clinical implications and functions of a novel antisense lncRNA PRKAG2-AS1 in hepatocellular carcinoma (HCC).Methods: PRKAG2-AS1 expression was examined in a cohort of 138 HCC patients by RT-qPCR. Overall survival (OS) and disease-free survival (DFS) analyses were presented based on PRKAG2-AS1 expression, followed by ROCs. After silencing PRKAG2-AS1, cell proliferation was assessed via CCK-8, colony formation and EdU staining assays. Migrated and invasive capacities were assessed by wound healing and transwell assays. The relationships between PRKAG2-AS1, miR-502-3p and BICD2 were validated by luciferase reporter, RIP and RNA pull-down assays. The expression and prognostic value of BICD2 were analyzed in TCGA database.Results: PRKAG2-AS1 was up-regulated in HCC than normal tissue specimens. High PRKAG2-AS1 expression was indicative of poorer OS and DFS time. Area under the curves (AUCs) for OS and DFS were 0.8653 and 0.7891, suggesting the well predictive efficacy of PRKAG2-AS1 expression. Targeting PRKAG2-AS1 distinctly inhibited proliferation, migration, and invasion in HCC cells. PRKAG2-AS1 was mainly expressed in cytoplasm of HCC cells. PRKAG2-AS1 may directly bind to the sites of miR-502-3p. Up-regulation of BICD2 was found in HCC tissues and associated with unfavorable prognosis. BICD2 was confirmed to be a downstream target of miR-502-3p. PRKAG2-AS1 could regulate miR-502-3p/BICD2 axis.Conclusion: Our findings identified a novel lncRNA PRKAG2-AS1 that was associated with clinical implications and malignant behaviors. Thus, PRKAG2-AS1 could become a promising therapeutic target.
Highlights
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally, occupying 75–80% among all liver cancer cases [1]
PRKAG2-AS1 was up-regulated in HCC than normal tissue specimens
Our findings identified a novel long non-coding RNAs (lncRNAs) PRKAG2-AS1 that was associated with clinical implications and malignant behaviors
Summary
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally, occupying 75–80% among all liver cancer cases [1]. The five-year survival rate is only 15–17% due to recurrence and metastasis [2]. Surgical resection followed by transcatheter arterial chemoembolization is the main therapeutic method [3]. Immune and targeted therapies have been widely given wide attention and exhibited favorable clinical outcomes [4, 5]. Only a small percentage of patients will benefit from the latest treatment strategies. Molecular target therapy is currently still limited [6]. Exploration of novel therapeutic targets is still of significance
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