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Long Non-Coding RNA PVT1 Promotes Doxorubicin Resistance by Inhibiting Ferroptosis in Breast Cancer
Dan Zhao1, Zheqiong Tan1, Weiqun Chen1,2,3
1Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, People's Republic of China.
Breast Cancer (Dove Medical Press)
|July 29, 2026
Summary
The long non-coding RNA PVT1 promotes doxorubicin resistance in breast cancer by inhibiting ferroptosis via SLC3A2. Silencing PVT1 restores sensitivity to doxorubicin, suggesting PVT1 as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer progression and therapeutic resistance.
- The lncRNA plasmacytoma variant translocation 1 (PVT1) has been implicated in breast cancer (BC) tumor growth and metastasis.
- Doxorubicin (DOX) resistance remains a significant challenge in BC treatment, necessitating research into resistance mechanisms.
Purpose of the Study:
- To investigate the role of PVT1 in doxorubicin resistance in breast cancer.
- To elucidate the underlying molecular mechanism by which PVT1 influences chemoresistance.
Main Methods:
- Gene and protein expression analyzed using qRT-PCR and Western blotting.
- Ferroptosis assessed via glutathione (GSH) and reactive oxygen species (ROS) levels.
- In vivo tumor models and transcriptome analysis were employed to validate mechanisms and identify targets.
Main Results:
- PVT1 was highly expressed in drug-resistant BC patient plasma and cell lines.
- Silencing PVT1 reduced GSH, increased ROS and lipid peroxidation, and enhanced DOX sensitivity in vivo.
- Transcriptomic analysis identified solute carrier family 3 member 2 (SLC3A2) as a key downstream target of PVT1.
Conclusions:
- PVT1 promotes doxorubicin resistance in BC by upregulating SLC3A2, thereby inhibiting ferroptosis.
- PVT1 represents a potential therapeutic target for overcoming doxorubicin resistance in breast cancer.
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