Related Experiment Video
Updated: Jun 10, 2025

Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
Published on: September 20, 2024
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.
Abstract:
Thyroid cancer (TC) is the most common malignant tumor of the head and neck. As a common epigenetic modification in mRNAs, N6-methyladenosine (m6A) modification plays critical roles in biological process of cancers. However, m6A methyltransferase methyltransferase-like 14 (METTL14)-mediated m6A modification and its potential regulatory mechanisms in TC are not fully elucidated. In our study, we observed that METTL14 was decreased in TC tissues and cells. And upregulation of METTL14 induced apoptotic cell death and hampered cell proliferation, epithelial mesenchymal transition (EMT) and tumor growth in vitro and in vivo. Mechanistically, METTL14 increased the expression of suppressor of cytokine signaling 3 (SOCS3) through m6A methylation modification, and knockdown of SOCS3 reversed the inhibitory effect of overexpressing METTL14 on TC tumorigenesis. In addition, METTL14-mediated m6A modification of SOCS3 inactivated the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway, and in the METTL14-overexpressing TC cells, silencing SOCS3-induced upregulation of cell proliferation, EMT and suppression of apoptosis was reversed by JAK2/STAT3 inhibitor AG490 and WP1066. Together, we indicated that METTL14/m6A/SOCS3/JAK2/STAT3 axis play an important role in the progression of TC.
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.
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Abnormal Proliferation
The JAK-STAT Signaling Pathway
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
PI3K/mTOR/AKT Signaling Pathway
TGF - β Signaling Pathway

