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Abstract
BackgroundHepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. However, the roles, functions, and working mechanisms of most lncRNAs in HCC remain poorly defined.MethodsReal-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of CCDC183-AS1 in HCC tissues and cell lines. Cell proliferation, migration and invasion ability were evaluated by CCK-8 and transwell assay, respectively. Animal experiments were used to explore the role of CCDC183-AS1 and miR-589-5p in vivo. Bioinformatic analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the regulatory relationship between CCDC183-AS1, miR-589-5p and SKP1.ResultsSignificantly upregulated expression of CCDC183-AS1 was observed in both HCC tissues and cell lines. HCC patients with higher expression of CCDC183-AS1 had a poorer overall survival rate. Functionally, overexpression of CCDC183-AS1 markedly promoted HCC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas the downregulation of CCDC183-AS1 exerted opposite effects. MiR-589-5p inhibitor counteracted the proliferation, migration and invasion inhibitory effects induced by CCDC183-AS1 silencing. Mechanistically, CCDC183-AS1 acted as a ceRNA through sponging miR-589-5p to offset its inhibitory effect on the target gene SKP1, then promoted the tumorigenesis of HCC.ConclusionsCCDC183-AS1 functions as an oncogene to promote HCC progression through the CCDC183-AS1/miR-589-5p/SKP1 axis. Our study provided a novel potential therapeutic target for HCC patients.
Highlights
Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide
We mainly focused on upregulated Long non-coding RNA (lncRNA) in HCC
We examined the results of our RNA sequencing and found 170 upregulated lncRNAs in HCC tissues relative to normal tissues (Supplementary Table 3). 15 lncRNAs were obtained by taking the intersection of 2 up-regulated lncRNA datasets mentioned above
Summary
Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. The therapeutic effects of HCC have been improved, including surgical resection, liver transplantation and radiofrequency ablation, the overall prognosis for HCC patients remains unsatisfactory due to the high rate of postoperative recurrence and metastasis [7, 8]. Further investigations of the molecular mechanisms underlying tumorigenesis and progression of HCC are urgently needed to develop more efficient therapeutic strategies [9]. Recent studies have indicated that lncRNA participates in cancer development and progression, affects the proliferation, apoptosis and metastasis of tumor cells [12]. The molecular and cellular mechanisms of lncRNAs in HCC have not been fully elucidated
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