Identifying CSNK1E as a therapeutic target in thyroid cancer among the core circadian clock genes

Shun-Yu Chi1, Yi-Chiung Hsu2,3,4, Chung-Hsin Tsai5,6

  • 1Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

PubMed

Insights

Altered circadian clock gene expression, including increased CSNK1E, is linked to thyroid cancer progression. Targeting CSNK1E with inhibitors suppressed thyroid cancer cell growth and tumor development in preclinical models.

Area of Science:

  • Molecular Biology
  • Oncology
  • Chronobiology

Background:

  • Thyroid malignancies are associated with altered circadian clock gene transcription.
  • Specific clock genes show differential expression during thyroid cancer progression and dedifferentiation.

Purpose of the Study:

  • To investigate the expression patterns of core circadian clock genes in thyroid neoplasms.
  • To evaluate the therapeutic potential of targeting casein kinase 1 epsilon (CSNK1E) in thyroid cancer.

Main Methods:

  • Screening of core circadian clock gene expression in thyroid neoplasms.
  • Immunohistochemical analysis of CSNK1E expression.
  • In vitro treatment of thyroid cancer cell lines with CSNK1E inhibitors (PF670462, IC261).
  • In vivo xenograft mouse models treated with IC261.

Main Results:

  • CSNK1E, NPAS2, and TIMELESS were upregulated; ARNTL, CRY1, CRY2, PER2, and RORA were downregulated in thyroid cancer.
  • Increased CSNK1E expression correlated with reduced tumor differentiation.
  • CSNK1E inhibitors inhibited cell growth, induced G2/M cell cycle arrest, and suppressed migration and invasion.
  • IC261 treatment significantly reduced tumor growth and proliferation in vivo.

Conclusions:

  • Aberrant CSNK1E expression is implicated in thyroid cancer dedifferentiation.
  • Targeting CSNK1E represents a promising therapeutic strategy for thyroid cancer.

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