Long noncoding RNA DIO3OS induces glycolytic-dominant metabolic reprogramming to promote aromatase inhibitor...

Area of Science:

• Oncology
• Molecular Biology
• Endocrinology

Background:

• Aromatase inhibitors (AIs) are standard endocrine therapy for postmenopausal ER-positive breast cancer.
• Resistance to AI therapy is a significant clinical challenge, leading to poor patient prognosis.
• Understanding the mechanisms of AI resistance is crucial for developing effective treatment strategies.

Purpose of the Study:

• To investigate the role of long noncoding RNA DIO3OS in AI-resistant breast cancer.
• To elucidate the molecular mechanisms by which DIO3OS contributes to AI resistance.
• To explore DIO3OS as a potential therapeutic target for overcoming AI resistance.

Main Methods:

• Analysis of AI-resistant breast tumors for metabolic and molecular changes.
• Investigating the effect of estrogen deprivation on DIO3OS expression in ER-positive breast cancer cells.
• Assessing the impact of DIO3OS on aerobic glycolysis and cell proliferation in vitro and in vivo.
• Identifying protein interactions of DIO3OS using molecular techniques.
• Quantifying lactate dehydrogenase A (LDHA) mRNA and protein levels.

Main Results:

• AI-resistant breast tumors exhibit enhanced aerobic glycolysis and upregulation of lncRNA DIO3OS.
• Long-term estrogen deprivation increases DIO3OS expression, promoting estrogen-independent proliferation.
• DIO3OS interacts with PTBP1 to stabilize LDHA mRNA, upregulating LDHA and activating glycolysis.
• DIO3OS upregulation correlates with poor prognosis in breast cancer patients receiving AI therapy.

Conclusions:

• lncRNA DIO3OS plays a critical role in regulating glycolytic metabolism in AI-resistant breast cancer.
• DIO3OS promotes estrogen-independent proliferation by enhancing aerobic glycolysis.
• Targeting DIO3OS presents a potential strategy to overcome AI resistance in ER-positive breast cancer.