ZIC1 is a putative tumor suppressor in thyroid cancer by modulating major signaling pathways and transcription factor

Wei Qiang1, Yuan Zhao, Qi Yang

  • 1Department of Endocrinology (W.Q., Q.Y., W.L., S.L., B.S., P.H.), The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, China; Department of Gerontology (Y.Z.), Shaanxi Provincial People's Hospital, Xi'an 710068, China; Department of Endocrinology and Metabolism (H.G.), The First Affiliated Hospital of China Medical University, Shenyang 110001, China; and Center for Translational Medicine (M.J.), The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.

Abstract

Insights

ZIC1 acts as a tumor suppressor in thyroid cancer, frequently inactivated by promoter hypermethylation. Its restoration inhibits cancer cell growth and metastasis by affecting key signaling pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • ZIC1 exhibits dual roles in cancer, acting as an oncogene in brain tumors but a tumor suppressor in gastric and colorectal cancers.
  • The function of ZIC1 in thyroid cancer pathogenesis was previously uncharacterized.

Purpose of the Study:

  • To elucidate the biological functions of ZIC1 in thyroid carcinogenesis.
  • To investigate the molecular mechanisms underlying ZIC1's role in thyroid cancer.

Main Methods:

  • Quantitative RT-PCR and methylation-specific PCR were employed to assess ZIC1 expression and promoter methylation.
  • Functional assays including cell proliferation, colony formation, cell cycle, apoptosis, migration, and invasion assays were conducted.

Main Results:

  • ZIC1 is frequently downregulated in thyroid cancer tissues and cell lines due to promoter hypermethylation.
  • ZIC1 hypermethylation correlates with lymph node metastasis in papillary thyroid cancer.
  • Restoring ZIC1 expression suppressed proliferation, colony formation, migration, and invasion, while inducing cell cycle arrest and apoptosis.

Conclusions:

  • ZIC1 functions as a tumor suppressor in thyroid cancer, inactivated by promoter hypermethylation.
  • ZIC1 modulates the PI3K/Akt and MAPK signaling pathways.
  • ZIC1 enhances FOXO3a transcriptional activity, contributing to its tumor-suppressive role.

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