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MiR-205-5p/GGCT Attenuates Growth and Metastasis of Papillary Thyroid Cancer by Regulating CD44

Han-Ning Li1,2,3, Hui-Min Zhang4, Xing-Rui Li1,2,3

  • 1Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei 430030, People's Republic of China.

Endocrinology
|February 25, 2022
PubMed

Insights

γ-glutamylcyclotransferase (GGCT) is upregulated in papillary thyroid cancer (PTC), driving tumor growth and metastasis. Targeting the novel miR-205-5p/GGCT/CD44 pathway offers potential therapeutic strategies for PTC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Papillary thyroid cancer (PTC) is the most common endocrine malignancy, but its pathogenesis remains unclear.
  • γ-glutamylcyclotransferase (GGCT), involved in glutathione homeostasis, is elevated in various tumors and is a potential therapeutic target.

Purpose of the Study:

  • To investigate the role of GGCT in PTC pathogenesis and progression.
  • To elucidate the signaling pathway involving GGCT in PTC.
  • To explore potential therapeutic strategies targeting the identified pathway.

Main Methods:

  • Bioinformatics analysis, immunohistochemistry, qRT-PCR, and Western blot assays were used to assess GGCT expression in PTC.
  • In vitro and in vivo experiments involving GGCT knockdown and microRNA-205-5p (miR-205-5p) delivery were performed.
  • Dual-luciferase reporter assays, RNA-RNA pull-down assays, co-immunoprecipitation, and immunohistochemistry were employed to confirm molecular interactions.

Main Results:

  • GGCT expression was significantly upregulated in PTC tissues and correlated with aggressive clinicopathological features and poor prognosis.
  • GGCT knockdown inhibited PTC cell growth and metastasis, reducing mesenchymal markers (N-cadherin, CD44, MMP2, MMP9) and increasing the epithelial marker (E-cadherin).
  • miR-205-5p directly targets GGCT, and its delivery reversed the pro-malignant effects of GGCT. GGCT was found to interact with and stabilize CD44.

Conclusions:

  • A novel signaling pathway, miR-205-5p/GGCT/CD44, is implicated in PTC carcinogenesis and progression.
  • Targeting GGCT or utilizing miR-205-5p mimics represents a promising therapeutic avenue for PTC treatment.
Keywords:
CD44GGCTPTCmiR-205-5p

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