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Published on: November 2, 2013
lncRNA POLR2J4 Plays a Biomarker Role in Hepatitis B Virus-Related Hepatocellular Carcinoma Through Regulating
Yimei Ji1, Xiaowei Chen2, Xin Liu3
1Department of Gastroenterology and Endoscopy, Third Affiliated Hospital of Naval Medical University, Shanghai, China.
Abstract:
Identifying novel therapeutic targets for hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) has become a key goal in liver cancer research. Even though long non-coding RNAs (lncRNAs) do not code proteins, they could regulate the expression of functional genes and thus mediate disease development. The aim of this study was to estimate the role of lncRNA POLR2J4 (POLR2J4) in the progression of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) to pinpoint a potential biomarker. This study included 109 patients diagnosed with HBV-positive HCC, from whom tissue samples were collected. The expression level of POLR2J4 was evaluated by qPCR. The significance of POLR2J4 in HBV-HCC development and prognosis was estimated by Chi-square, Kaplan-Meier, and Cox analysis. In vitro, POLR2J4 was regulated in HBV-HCC cells, and its effect on cell growth and metastasis was assessed by CCK8 and Transwell assay. The interaction between POLR2J4 and miR-214-3p was evaluated through the luciferase reporter and RNA immunoprecipitation assays. In tumor tissues of HBV-HCC patients, there was an observed increase in the expression of POLR2J4. The increase was closely related with patients' presence of cirrhosis and vascular invasion, higher AFP, and advanced Edmondson grade and TNM stage. An upregulation of POLR2J4 predicted a poor prognosis for HBV-HCC patients and served as an independent indicator. In HBV-related HCC cells, silencing POLR2J4 suppressed cell proliferation, migration, and invasion. Furthermore, POLR2J4 negatively regulated miR-214-3p reversing the inhibition of cellular processes. POLR2J4 acted as a prognostic biomarker and a tumor promoter of HBV-HCC by modulating miR-214-3p.
Insights
Long non-coding RNA POLR2J4 (POLR2J4) promotes hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) progression. Upregulated POLR2J4 indicates poor prognosis and drives tumor growth by regulating miR-214-3p.
Area of Science:
- Hepatology and Oncology
- Molecular Biology
- Cancer Research
Background:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge, particularly when associated with hepatitis B virus (HBV) infection.
- Long non-coding RNAs (lncRNAs) are emerging as critical regulators of gene expression and play roles in various diseases, including cancer.
- Identifying novel biomarkers and therapeutic targets for HBV-induced HCC is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the role of lncRNA POLR2J4 (POLR2J4) in the progression of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC).
- To evaluate POLR2J4 as a potential diagnostic and prognostic biomarker for HBV-HCC.
- To elucidate the molecular mechanism by which POLR2J4 influences HBV-HCC development.
Main Methods:
- Quantitative real-time PCR (qPCR) to assess POLR2J4 expression in 109 HBV-HCC patient tissues.
- Statistical analyses including Chi-square, Kaplan-Meier, and Cox regression for prognostic evaluation.
- In vitro experiments using CCK8 and Transwell assays to determine the effects of POLR2J4 on cell proliferation, migration, and invasion in HBV-HCC cells.
- Luciferase reporter and RNA immunoprecipitation assays to investigate the interaction between POLR2J4 and miR-214-3p.
Main Results:
- POLR2J4 expression was significantly upregulated in HBV-HCC tumor tissues compared to normal tissues.
- Increased POLR2J4 levels correlated with clinical parameters such as cirrhosis, vascular invasion, elevated AFP, and advanced TNM stage.
- Upregulation of POLR2J4 was an independent predictor of poor prognosis in HBV-HCC patients.
- Silencing POLR2J4 suppressed proliferation, migration, and invasion of HBV-HCC cells.
- POLR2J4 was found to negatively regulate miR-214-3p, thereby promoting cellular processes.
Conclusions:
- lncRNA POLR2J4 serves as a tumor promoter in HBV-HCC.
- POLR2J4 is a potential prognostic biomarker for HBV-HCC.
- The oncogenic role of POLR2J4 in HBV-HCC is mediated through the modulation of miR-214-3p.
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