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AUF1 Promotes Proliferation and Invasion of Thyroid Cancer via Downregulation of ZBTB2 and Subsequent TRIM58

Xin Du1, Jia-Mei Wang2, Da-Lin Zhang3

  • 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, Shenyang, China.

Frontiers in Oncology
|July 5, 2021
PubMed

Insights

AUF1 knockdown increases TRIM58 and ZBTB2 in papillary thyroid cancer cells. Inhibiting these genes promotes cancer cell proliferation, migration, and invasion, revealing AUF1

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Papillary thyroid cancer (PTC) pathogenesis is not fully understood, limiting therapeutic options for invasive cases.
  • AUF1's role in thyroid cancer progression is known, but its molecular mechanisms require elucidation.

Purpose of the Study:

  • To investigate the molecular mechanism by which AUF1 influences thyroid cancer progression.
  • To explore the relationship between AUF1, TRIM58, and ZBTB2 in PTC cells.

Main Methods:

  • Utilized CRISPR/Cas9 to knockdown AUF1 in IHH4 and TPC1 papillary thyroid cancer cell lines.
  • Employed small hairpin RNAs (shRNAs) to inhibit TRIM58 and ZBTB2 expression.
  • Identified specific binding sites for ZBTB2 on the TRIM58 promoter and AUF1 on the ZBTB2 3'-UTR.

Main Results:

  • AUF1 knockdown led to increased expression of TRIM58 and ZBTB2 in PTC cells.
  • Inhibition of TRIM58 or ZBTB2 in AUF1-knockdown cells enhanced proliferation, migration, and invasion.
  • Specific binding interactions between ZBTB2, TRIM58, AUF1, and ZBTB2 were identified.

Conclusions:

  • AUF1 regulates papillary thyroid cancer cell behavior through the modulation of ZBTB2 and TRIM58 expression.
  • The findings elucidate a novel molecular pathway involving AUF1, ZBTB2, and TRIM58 in PTC pathogenesis.
Keywords:
AUF1TRIM58ZBTB2papillary thyroid cancerproliferation and invasion

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