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Inflammatory cytokine-regulated LNCPTCTS suppresses thyroid cancer progression via enhancing Snail nuclear export

Chi Ma1, Nasha Zhang2, Teng Wang3

  • 1Department of Thyroid Surgery, Yantai Yuhuangding Hospital, Shandong University, Yantai 264000, Shandong Province, China; Shandong University Cancer Center, Jinan 250117, Shandong Province, China.

Cancer Letters
|September 23, 2023
PubMed

Insights

Thyroid cancer's spread to lymph nodes is linked to reduced expression of a tumor-suppressing lncRNA (LNCPTCTS). Inflammatory cytokines decrease LNCPTCTS, promoting cancer progression and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Lymph node metastases are common in cancers, driving progression and poor outcomes.
  • Thyroid cancer frequently metastasizes to lymph nodes, but the underlying mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the role of epigenetic reprogramming in thyroid cancer lymph node metastasis.
  • To identify novel molecular players involved in thyroid cancer progression and metastasis.

Main Methods:

  • Analysis of lncRNA expression in thyroid cancer tissues and metastatic lymph nodes.
  • Investigating the regulation of LNCPTCTS by inflammatory cytokines (TNFα, CXCL10) and transcription factors (EGR1).
  • Studying the interaction of LNCPTCTS with eEF1A2 and Snail, and its effect on Snail nuclear export and downstream targets.

Main Results:

  • LNCPTCTS is a novel tumor-suppressive lncRNA with significantly decreased expression in thyroid cancer, especially in metastatic lymph nodes.
  • Inflammatory cytokines TNFα and CXCL10 reduce LNCPTCTS expression by impairing EGR1 binding to its promoter.
  • Loss of LNCPTCTS promotes Snail nuclear accumulation, suppresses E-cadherin and PEBP1, activating epithelial-mesenchymal transition and MAPK signaling.

Conclusions:

  • A novel paradigm links the tumor microenvironment (TME) and epigenetic reprogramming in thyroid cancer cells, driving lymph node metastasis.
  • LNCPTCTS acts as a crucial regulator, and its decreased expression facilitates cancer spread.
  • LNCPTCTS represents a potential targetable vulnerability for treating thyroid cancer metastasis.
Keywords:
Inflammatory cytokineNuclear exportPapillary thyroid carcinomaSnaileEF1A2lncRNA

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