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Updated: Jun 13, 2026

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

Nucleolar and spindle-associated protein 1 (NUSAP1) promotes thyroid cancer dedifferentiation via BCAT1-mediated

Yue Wang1, Guorong Wang1, Xuzi Zhao2

  • 1Thyroid Surgery Department, The Second Hospital of Dalian Medical University, Dalian, 116023, China.

International Journal of Biological Macromolecules
|June 11, 2026
PubMed

Insights

Nucleolar and spindle-associated protein 1 (NUSAP1) drives thyroid cancer dedifferentiation by altering amino acid metabolism and gene expression. Inhibiting NUSAP1 offers a potential new treatment strategy for thyroid cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Thyroid cancer (TC) dedifferentiation is linked to poor prognosis and treatment resistance.
  • The molecular drivers of TC dedifferentiation are not fully understood.
  • Identifying key molecules is crucial for developing targeted therapies.

Purpose of the Study:

  • To identify critical molecules involved in thyroid cancer dedifferentiation.
  • To elucidate the molecular mechanisms underlying NUSAP1-mediated dedifferentiation.
  • To explore NUSAP1 as a potential therapeutic target in TC.

Main Methods:

  • Integrated analysis to screen for key molecules in TC dedifferentiation.
  • RNA sequencing enrichment analysis to identify mechanistic pathways.
  • Investigation of NUSAP1's role in cell proliferation, migration, and differentiation.
  • Assessment of NUSAP1's interaction with BRD4 and its effect on BCAT1 transcription.
  • Analysis of the impact on branched-chain amino acid (BCAA) catabolism and epigenetic modifications.

Main Results:

  • NUSAP1 is overexpressed in TC and associated with poor prognosis.
  • NUSAP1 upregulation promotes TC cell proliferation, migration, and dedifferentiation.
  • NUSAP1 forms a complex with BRD4, activating BCAT1 transcription and BCAA catabolism.
  • This leads to reduced α-ketoglutarate (α-KG) and increased H3K27me3, suppressing differentiation genes.
  • Pharmacologic inhibition of NUSAP1 with entinostat showed promising results.

Conclusions:

  • NUSAP1 promotes TC dedifferentiation via the BCAT1/α-KG/H3K27me3 pathway.
  • NUSAP1 acts in concert with BRD4 to regulate key metabolic and epigenetic events.
  • NUSAP1 represents a promising therapeutic target for thyroid cancer treatment.
Keywords:
BCAT1DedifferentiationNUSAP1Thyroid cancerα-KG

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