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YAP/miR-524-5p axis negatively regulates TXNIP expression to promote chondrosarcoma cell growth

Ri-Xu Liu1, Wang Tang1, Bo-Yuan Zheng1

  • 1Center for Joint Surgery and Sports Medicine, The First Affiliated Hospital, Jinan University, Guangzhou, 510630, China; Institute of Orthopedic Diseases & the Bone and Joint Disease Institute of Guangdong-Hong Kong-Macao Greater Bay Area, Jinan University, Guangzhou, 510630, China.

Biochemical and Biophysical Research Communications
|December 30, 2021
PubMed

Insights

Thioredoxin interacting protein (TXNIP) acts as a tumor suppressor in chondrosarcoma (CHS). The YAP/miRNA-524-5p/TXNIP pathway regulates CHS cell growth and offers potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Chondrosarcoma (CHS) is a common bone cancer with limited treatment options.
  • Thioredoxin interacting protein (TXNIP) is implicated in bone sarcoma oncogenesis.
  • The role of TXNIP in CHS progression is currently under investigation.

Purpose of the Study:

  • To investigate the role of TXNIP in chondrosarcoma (CHS) development.
  • To elucidate the regulatory mechanisms of TXNIP expression in CHS.
  • To identify potential therapeutic targets for CHS.

Main Methods:

  • TXNIP knockdown in CHS cells to assess proliferation and metabolism.
  • Yeast-two hybrid assays and co-immunoprecipitation to study YAP-TXNIP interaction.
  • Quantitative real-time PCR and Western blotting to analyze gene and protein expression.
  • In vitro and in vivo experiments to validate findings.

Main Results:

  • TXNIP knockdown enhanced CHS cell proliferation by increasing glycolytic metabolism (Warburg effect).
  • Yeast-two hybrid assays revealed YAP functions as an upstream regulator of TXNIP.
  • YAP negatively modulated TXNIP mRNA and protein expression both in vitro and in vivo.
  • miRNA-524-5p was identified as a crucial mediator in the YAP-regulated TXNIP expression pathway.
  • No direct interaction was observed between YAP and TXNIP.

Conclusions:

  • TXNIP functions as a tumor suppressor in chondrosarcoma.
  • The YAP/miRNA-524-5p/TXNIP signaling axis plays a significant role in CHS cell growth.
  • This pathway represents a potential novel therapeutic strategy for chondrosarcoma.
Keywords:
ChondrosarcomaGlycolysisTXNIPYAPmiR-524-5p

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