METTL14-mediated m6A modification upregulated SOCS3 expression alleviates thyroid cancer progression by regulating the JAK2/STAT3 pathway

• Published in: Molecular and cellular probes 2024-12, Vol.78, p.101987, Article 101987
• Main Authors: Zhou, Ming, Zhang, Yaqi, Zhang, Qiong, Tong, Yanchu
• Format: Article
• Language: English
• Subjects: Methyltransferase-like 14 (METTL14); N6-methyladenosine (m6A); Suppressor of cytokine signaling 3 (SOCS3); Thyroid cancer
• ISSN: 0890-8508; 1096-1194; 1096-1194
• DOI: 10.1016/j.mcp.2024.101987

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. •Upregulation of METTL14 alleviates thyroid cancer progression by inhibiting proliferation, EMT, and promoting apoptosis.•METTL14-mediated m6A modification upregulates SOCS3 expression.•METTL14-modified SOCS3 inhibits tumorigenesis of thyroid cancer by regulating JAK2/STAT3 signaling pathway.