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.

Molecular Metabolism
|July 26, 2021
PubMed
Abstract

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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