METTL14-mediated m6A modification upregulated SOCS3 expression alleviates thyroid cancer progression by regulating

Ming Zhou1, Yaqi Zhang2, Qiong Zhang3

  • 1Department of Thyroid Vascular Surgery, Jingzhou Central Hospital, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, 434000, China.

PubMed

Insights

Methyltransferase-like 14 (METTL14) is reduced in thyroid cancer (TC). Increasing METTL14 inhibits TC progression by regulating the SOCS3/JAK2/STAT3 pathway, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Thyroid cancer (TC) is the most common head and neck malignancy.
  • N6-methyladenosine (m6A) modification is a key epigenetic regulator in cancer.
  • The role of METTL14-mediated m6A in TC is not fully understood.

Purpose of the Study:

  • To investigate the function and mechanism of METTL14 in thyroid cancer progression.
  • To elucidate the regulatory pathway involving METTL14, m6A, SOCS3, and the JAK2/STAT3 signaling pathway in TC.

Main Methods:

  • Analysis of METTL14 expression in TC tissues and cells.
  • In vitro and in vivo experiments to assess the effects of METTL14 upregulation on TC cells.
  • Investigation of the molecular mechanism involving m6A modification, SOCS3 expression, and the JAK2/STAT3 pathway.
  • Utilized JAK2/STAT3 inhibitors (AG490, WP1066) to validate the pathway.

Main Results:

  • METTL14 expression was significantly decreased in TC tissues and cells.
  • METTL14 upregulation suppressed TC cell proliferation, epithelial-mesenchymal transition (EMT), and tumor growth, while inducing apoptosis.
  • METTL14 promoted SOCS3 expression via m6A modification, which in turn inactivated the JAK2/STAT3 pathway.
  • Knockdown of SOCS3 or activation of the JAK2/STAT3 pathway reversed the inhibitory effects of METTL14.

Conclusions:

  • METTL14 acts as a tumor suppressor in thyroid cancer.
  • The METTL14/m6A/SOCS3/JAK2/STAT3 axis is a critical regulator of TC progression.
  • METTL14 represents a potential therapeutic target for thyroid cancer treatment.

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