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Updated: Oct 26, 2025

The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia
Published on: November 30, 2016
Novel noncoding RNA CircPTK2 regulates lipolysis and adipogenesis in cachexia
Zuoyou Ding1, Diya Sun1, Jun Han1
1Department of General Surgery, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, People's Republic of China.
Objective:
Cancer-associated cachexia is a devastating pathological disorder characterized by skeletal muscle wasting and fat storage depletion. Circular RNA, a newly discovered class of noncoding RNAs with important roles in regulating lipid metabolism, has not been fully understood in the pathology of cachexia. We aimed to identify circular RNAs that are upregulated in adipose tissues from cachectic patients and explore their function and mechanism in lipid metabolism.
Methods:
Whole transcriptome RNA sequencing was used to screen for differentially expressed circRNAs. Quantitative reverse transcription PCR was applied to detect the expression level of circPTK2 in adipose tissues. The diagnostic value of circPTK2 was evaluated in adipose tissues from patients with and without cachexia. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circPTK2 on lipolysis and adipogenesis. Mechanistically, luciferase reporter assay, RNA immunoprecipitation, and fluorescent in situ hybridization were performed to confirm the interaction between circPTK2 and miR-182-5p in adipocytes.
Results:
We detected 66 differentially expressed circular RNA candidates and proved that circPTK2 was upregulated in adipose tissues from cachectic patients. Then we identified that circPTK2 was closely related to the pathological process of cachexia and could be used as a diagnostic marker. Mechanistically, circPTK2 bound competitively to miR-182-5p and abrogated the suppression on its target gene JAZF1, which finally led to promotion of lipolysis and inhibition of adipogenesis. In vivo experiments demonstrated that overexpression of circPTK2 inhibited adipogenesis and enhanced lipolysis.
Conclusions:
Our findings reveal the novel role of circPTK2 in promoting lipolysis and reducing adipogenesis via a ceRNA mechanism and provide a potential diagnostic biomarker and therapeutic target for cancer-associated cachexia.
Insights
Circular RNA circPTK2 is upregulated in cancer cachexia, promoting fat loss by inhibiting adipogenesis and enhancing lipolysis. This study identifies circPTK2 as a potential diagnostic marker and therapeutic target for this condition.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Cancer-associated cachexia involves skeletal muscle wasting and fat depletion.
- Circular RNAs (circRNAs) regulate lipid metabolism, but their role in cachexia is unclear.
- Identifying cachexia-specific circRNAs is crucial for understanding and treating the condition.
Purpose of the Study:
- To identify circRNAs upregulated in adipose tissue of cachectic patients.
- To investigate the function and mechanism of identified circRNAs in lipid metabolism.
- To explore circPTK2 as a diagnostic biomarker and therapeutic target for cancer cachexia.
Main Methods:
- Whole transcriptome RNA sequencing to screen for differentially expressed circRNAs.
- Quantitative reverse transcription PCR to validate circPTK2 expression.
- In vitro and in vivo experiments to assess circPTK2's effects on lipolysis and adipogenesis.
- Mechanistic studies including luciferase reporter assays and RNA immunoprecipitation to elucidate molecular interactions.
Main Results:
- Identified 66 differentially expressed circRNA candidates, with circPTK2 significantly upregulated in cachectic adipose tissue.
- circPTK2 acts as a diagnostic marker for cachexia.
- circPTK2 promotes lipolysis and inhibits adipogenesis by sponging miR-182-5p, thereby upregulating JAZF1.
- In vivo studies confirmed circPTK2's role in modulating adipogenesis and lipolysis.
Conclusions:
- circPTK2 plays a novel role in promoting lipolysis and reducing adipogenesis through a competing endogenous RNA (ceRNA) mechanism.
- circPTK2 represents a potential diagnostic biomarker for cancer-associated cachexia.
- circPTK2 emerges as a promising therapeutic target for managing cancer cachexia.
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