Dataset Information

LncRNA PCBP1-AS1 Aggravates the Progression of Hepatocellular Carcinoma via Regulating PCBP1/PRL-3/AKT Pathway.

ABSTRACT: Background:Hepatocellular carcinoma (HCC) is a very belligerent primary liver tumor with high metastatic potential. Aberrant expression of lncRNAs drives tumorous invasion and metastasis. Whether lncRNAs engage mechanisms of liver cancer metastasis remains largely unexplored. Patients and Methods:We collected HCC tissues from the tumors and their adjacent normal samples in the Chinese population and analyzed the levels of lncRNAs by microarray analysis. The gain- and loss-of-function analysis demonstrated that PCBP1-AS1 accelerated tumorous growth and metastasis in vivo and in vitro. Moreover, we used RNA-pulldown assay to show that PCBP1-AS1 physically interacted with polyC-RNA-binding protein 1 (PCBP1); meanwhile, PCBP1-AS1 was indeed detected in RIP with the PCBP1 antibody. Mechanistically, we first explored the relationship between PCBP1-AS1 and PCBP1 in HCC cell lines. Results:Here we show that PCBP1-AS1, identified by microarray analysis on pre- and post-operative HCC plasma specimens, was highly expressed in human HCC, clinically verified as a prometastatic factor and markedly associated with poor prognosis in patients with hepatocellular carcinoma. PCBP1-AS1 was negatively related with PCBP1 at the messenger RNA and protein expression levels. PCBP1-AS1 triggered PRL-3 and AKT in HCC tumor cells. Additionally, the double knockout of PCBP1 and PCBP1-AS1 abolished the PCBP1-AS1-induced PRL-3-AKT signalling pathway activation. Conclusion:The upregulation of PCBP1-AS1 enhances proliferation and metastasis in HCC, thus regulating the PCBP1-PRL-3-AKT signalling pathway.

SUBMITTER: Luo T

PROVIDER: S-EPMC7352448 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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lncRNA PCBP1-AS1 Aggravates the Progression of Hepatocellular Carcinoma via Regulating PCBP1/PRL-3/AKT Pathway.

Luo Tianping T Gao Yuan Y Zhangyuan Guangyan G Xu Xiaoliang X Xue Cailin C Jin Lei L Zhang Wenjie W Zhu Chunfu C Sun Beicheng B Qin Xihu X

Cancer management and research 20200706

<h4>Background</h4>Hepatocellular carcinoma (HCC) is a very belligerent primary liver tumor with high metastatic potential. Aberrant expression of lncRNAs drives tumorous invasion and metastasis. Whether lncRNAs engage mechanisms of liver cancer metastasis remains largely unexplored.<h4>Patients and methods</h4>We collected HCC tissues from the tumors and their adjacent normal samples in the Chinese population and analyzed the levels of lncRNAs by microarray analysis. The gain- and loss-of-funct ...[more]

PMID: 32753957

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Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Increasing evidence revealed that long noncoding RNAs (lncRNAs) were frequently involved in various malignancies. Here, we explored the clinical significances, roles, and mechanisms of lncRNA ADORA2A antisense RNA 1 (ADORA2A-AS1) in HCC.MethodsThe clinical significances of ADORA2A-AS1 in HCC were analyzed using RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) project. The expressions of ADORA2A-AS1, Fascin Actin-Bundling Protein 1 (FSCN1), Matrix Metallopeptidase 2 (MMP2), and Baculoviral IAP Repeat Containing 7 (BIRC7) in HCC tissues and cells were measured by qRT-PCR. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), caspase-3 activity assay, transwell migration and invasion assays, and xenograft growth and metastasis experiments were performed to evaluate the roles of ADORA2A-AS1 in HCC. RNA pull-down, RNA immunoprecipitation, qRT-PCR, Western blot, and RNA stability assay were performed to elucidate the mechanisms of ADORA2A-AS1 in HCC.ResultsADORA2A-AS1 was identified as an HCC-related lncRNA, whose low expression was correlated with advanced stage and poor outcome in HCC. Gain- and loss-of functional experiments demonstrated that ADORA2A-AS1 inhibited HCC cell proliferation, induced cell apoptosis, repressed cell migration and invasion, and repressed xenograft growth and metastasis in vivo. Mechanistically, ADORA2A-AS1 competitively bound HuR (Hu Antigen R), repressed the binding of HuR to FSCN1 transcript, decreased FSCN1 transcript stability, and downregulated FSCN1 expression. The expression of FSCN1 was negatively correlated with ADORA2A-AS1 in HCC tissues. Through downregulating FSCN1, ADORA2A-AS1 repressed AKT pathway activation. Functional rescue assays showed that blocking of FSCN1/AKT axis abrogated the roles of ADORA2A-AS1 in HCC.ConclusionLow-expression ADORA2A-AS1 is correlated with poor survival of HCC patients. ADORA2A-AS1 exerts tumor-suppressive roles in HCC via binding HuR and repressing FSCN1/AKT axis.

Dataset Information

LncRNA PCBP1-AS1 Aggravates the Progression of Hepatocellular Carcinoma via Regulating PCBP1/PRL-3/AKT Pathway.

Publications

lncRNA PCBP1-AS1 Aggravates the Progression of Hepatocellular Carcinoma via Regulating PCBP1/PRL-3/AKT Pathway.

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