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Updated: May 9, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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Targeting HCG18 counteracts ferroptosis resistance via blocking the miR-30a-5p/RRM2/GSS pathway in hepatocellular
Tian Zhan1, Yawei Liu2, Shuoke Duan3,4
1Department of General Surgery, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China.
Abstract:
Background: Finding effective strategies and novel targets for reversing drug resistance is one of the major frontiers in hepatocellular carcinoma (HCC) research. Ferroptosis is participate in the malignant progression and drug resistance of HCC. However, the underlying molecular mechanisms remail largely uninvestigated. Methods: HCC cell lines and xenografted nude mice were used as experimental models. Biological functions were investigated by various molecular biology experiments. An HCC population was used to reveal clinical significance. Results: In our study, HCG18 and RRM2 was found to be associated with unfavorable prognosis. HCG18 regulates RRM2 expression through competitively binding to miR-30a-5p, consequently impacting ferroptosis. RRM2 directly regulated GSS to increase GSH synthesis. The colony formation assay demonstrated that overexpression of HCG18 inhibited erastin-induced cell death. In addition, in vivo experiments have also confirmed that HCG18 can inhibit ferroptosis by regulating the expression of RRM2, thereby promoting HCC proliferation. Conclusion: Our study discovered a novel lncRNA HCG18, as a "switch-like" molecule of the axis of miR-30a-5p/RRM2/GSS, confers resistance to ferroptosis and holds promise as a potential target for ferroptosis-dependent therapy.
Insights
Researchers identified a new molecule, HCG18, that helps hepatocellular carcinoma (HCC) cells resist ferroptosis, a cell death process. This finding offers a potential new target for developing therapies to overcome drug resistance in HCC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Drug resistance is a major challenge in hepatocellular carcinoma (HCC) treatment.
- Ferroptosis, a form of regulated cell death, plays a role in HCC progression and drug resistance.
- The molecular mechanisms underlying ferroptosis regulation in HCC remain largely unknown.
Purpose of the Study:
- To investigate the role of HCG18 in hepatocellular carcinoma (HCC).
- To elucidate the molecular mechanisms by which HCG18 influences ferroptosis.
- To identify potential therapeutic targets for overcoming drug resistance in HCC.
Main Methods:
- Utilized HCC cell lines and xenografted nude mouse models.
- Conducted various molecular biology experiments to assess biological functions.
- Analyzed an HCC patient population to determine clinical significance.
Main Results:
- HCG18 and RRM2 expression correlated with poor prognosis in HCC patients.
- HCG18 targets miR-30a-5p to regulate RRM2 expression, impacting ferroptosis.
- RRM2 regulates GSS and glutathione synthesis, promoting HCC proliferation and inhibiting erastin-induced cell death.
Conclusions:
- Identified HCG18 as a novel long non-coding RNA involved in HCC.
- Established the miR-30a-5p/RRM2/GSS axis as a key regulator of ferroptosis in HCC.
- HCG18 acts as a switch conferring resistance to ferroptosis, presenting a promising therapeutic target for HCC.
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