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Targeting glycolytic reprogramming by tsRNA-0032 for treating pathological lymphangiogenesis
Fan Ye1,2, Ziran Zhang1, Lianjun Shi1
1The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.
Small RNA tsRNA-0032 inhibits lymphangiogenesis by targeting PKM2 glycolysis, offering therapeutic potential for diseases linked to abnormal blood vessel growth.
Area of Science:
- Molecular Biology
- Cell Biology
- Physiology
Background:
- Lymphangiogenesis is crucial for maintaining tissue fluid balance, immune responses, and nutrient absorption.
- Dysfunctional lymphangiogenesis is associated with various pathologies, including cancer, inflammation, and autoimmune disorders.
- Understanding the molecular regulators of lymphangiogenesis is essential for developing therapeutic strategies.
Purpose of the Study:
- To investigate the role and molecular mechanism of tsRNA-0032 in regulating lymphangiogenesis.
- To explore the potential of tsRNA-0032 as a therapeutic target for lymphangiogenesis-related diseases.
Main Methods:
- Assessed tsRNA-0032 expression in corneal suture and human lymphatic endothelial cell (HLEC) models under inflammatory conditions.
- Investigated the effects of tsRNA-0032 overexpression on HLEC proliferation, migration, and tube formation.
- Examined the interaction of tsRNA-0032 with Ago2 protein and its impact on glycolysis by targeting PKM2.
- Analyzed clinical data comparing tsRNA-0032 and PKM2 levels in corneal tissues of transplant recipients and donors.
Main Results:
- tsRNA-0032 expression was significantly reduced in inflammatory models and in corneal tissues of transplant recipients.
- Overexpression of tsRNA-0032 inhibited HLEC functions and corneal lymphangiogenesis.
- tsRNA-0032 interacts with Ago2, reduces ATP production, and lowers pyruvate/lactate levels by targeting PKM2, thus regulating glycolysis.
- Clinical data showed decreased tsRNA-0032 and increased PKM2 in transplant recipients, indicating a relevant tsRNA-0032/PKM2 axis.
Conclusions:
- tsRNA-0032 acts as an anti-lymphangiogenic factor by modulating cellular energy metabolism through the PKM2/glycolysis pathway.
- The tsRNA-0032/PKM2 axis is clinically relevant in corneal lymphangiogenesis.
- tsRNA-0032 represents a potential therapeutic target for managing lymphangiogenesis in related diseases.
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