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Updated: Oct 26, 2025

Use of Alu Element Containing Minigenes to Analyze Circular RNAs
Published on: March 10, 2020
Circular RNA circUBE2D2 functions as an oncogenic factor in hepatocellular carcinoma sorafenib resistance and
Hai Huang1, Jian Peng2, Shijian Yi3
1Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Wuming Hospital Nanning 530199, China.
Abstract:
Circular RNAs (circRNAs) have been reported to regulate the hepatocellular carcinoma (HCC) chemoresistance and tumor progression by regulating gene expression. However, the underlying molecular mechanisms of HCC sorafenib resistance regulated by circRNAs remain unclear. Here, higher expression of circUBE2D2 was directly associated with low survival rate in HCC patients. Functional experiments showed that circUBE2D2 promoted the glycolysis (Warburg effect) and sorafenib resistance in vitro, and knockdown of circUBE2D2 repressed the tumor growth in vivo. Mechanistically, circUBE2D2 was predominantly localized in the cytoplasm and sponged miR-889-3p, which in turn targeted the 3'-UTR of LDHA mRNA. Therefore, circUBE2D2 exerted an oncogenic role through miR-889-3p/LDHA axis. In conclusion, these findings demonstrate that circUBE2D2 accelerated the HCC glycolysis and sorafenib resistance via circUBE2D2/miR-889-3p/LDHA axis, which provides a novel approach for HCC treatment.
Insights
Circular RNAs (circRNAs) promote hepatocellular carcinoma (HCC) glycolysis and sorafenib resistance by regulating the miR-889-3p/LDHA axis. Targeting circUBE2D2 offers a potential new strategy for HCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Circular RNAs (circRNAs) influence hepatocellular carcinoma (HCC) progression and chemoresistance.
- The specific molecular mechanisms of circRNA-mediated sorafenib resistance in HCC are not fully understood.
Purpose of the Study:
- To investigate the role of circUBE2D2 in HCC sorafenib resistance and tumor progression.
- To elucidate the underlying molecular mechanism involving the miR-889-3p/LDHA axis.
Main Methods:
- Correlation analysis between circUBE2D2 expression and HCC patient survival.
- In vitro functional assays to assess the impact of circUBE2D2 on glycolysis and sorafenib resistance.
- In vivo tumor growth experiments following circUBE2D2 knockdown.
- Mechanism studies involving circRNA localization, microRNA sponging, and mRNA targeting.
Main Results:
- Elevated circUBE2D2 expression correlates with reduced survival rates in HCC patients.
- circUBE2D2 promotes glycolysis (Warburg effect) and sorafenib resistance in vitro.
- Knockdown of circUBE2D2 inhibits tumor growth in vivo.
- circUBE2D2 acts as a molecular sponge for miR-889-3p, leading to increased LDHA expression.
Conclusions:
- circUBE2D2 accelerates HCC glycolysis and sorafenib resistance through the circUBE2D2/miR-889-3p/LDHA pathway.
- This pathway represents a novel therapeutic target for overcoming sorafenib resistance in HCC.
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