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TRIM26 promotes non-small cell lung cancer survival by inducing PBX1 degradation

Yuening Sun1,2, Peng Lin3, Xiumin Zhou4

  • 1Guangdong Institute of Cardiovascular Diseases, Guangdong Key Laboratory of Vascular Diseases, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511436, P. R. China.

International Journal of Biological Sciences
|June 16, 2023
PubMed

Insights

The transcription factor PBX1 inhibits non-small cell lung cancer (NSCLC) growth, while the ubiquitin ligase TRIM26 promotes it by degrading PBX1. TRIM26 may be a therapeutic target for NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The transcription factor PBX1 is implicated as an oncogene in several cancers.
  • Its specific role and mechanism in non-small cell lung cancer (NSCLC) remain unclear.

Purpose of the Study:

  • To investigate the function of PBX1 in NSCLC.
  • To elucidate the regulatory mechanism of PBX1 in NSCLC.
  • To identify potential therapeutic targets for NSCLC.

Main Methods:

  • Affinity purification coupled with tandem mass spectrometry (MS/MS).
  • Western blotting to detect protein levels and ubiquitination.
  • Gene expression analysis.
  • Cell proliferation, migration, and colony formation assays.
  • NSCLC xenograft models.

Main Results:

  • PBX1 is downregulated in NSCLC tissues and inhibits cell proliferation and migration.
  • The ubiquitin ligase TRIM26 binds to PBX1, mediating its K48-linked polyubiquitination and proteasomal degradation.
  • TRIM26 promotes NSCLC proliferation, colony formation, and migration, and is highly expressed in NSCLC tissues, predicting poor prognosis.
  • Overexpression of TRIM26 promotes NSCLC xenograft growth, while TRIM26 knockout suppresses it.

Conclusions:

  • TRIM26 acts as a ubiquitin ligase for PBX1, promoting NSCLC tumor growth.
  • PBX1 inhibits NSCLC tumor growth.
  • TRIM26 represents a potential novel therapeutic target for NSCLC treatment.
Keywords:
Non-small cell lung cancerPre-B cell leukemia transcription factor 1Tripartite motif containing 26

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