METTL14-mediated m6A modification upregulated SOCS3 expression alleviates thyroid cancer progression by regulating the JAK2/STAT3 pathway
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 modi...
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Elsevier
2024-12-01
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| Series: | Molecular and Cellular Probes |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0890850824000392 |
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| author | Ming Zhou Yaqi Zhang Qiong Zhang Yanchu Tong |
| author_facet | Ming Zhou Yaqi Zhang Qiong Zhang Yanchu Tong |
| author_sort | Ming Zhou |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-23fc2af8d82c4ffdb4c89aa60f858f8d |
| institution | Kabale University |
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| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
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| series | Molecular and Cellular Probes |
| spelling | doaj-art-23fc2af8d82c4ffdb4c89aa60f858f8d2024-12-17T04:58:48ZengElsevierMolecular and Cellular Probes0890-85082024-12-0178101987METTL14-mediated m6A modification upregulated SOCS3 expression alleviates thyroid cancer progression by regulating the JAK2/STAT3 pathwayMing Zhou0Yaqi Zhang1Qiong Zhang2Yanchu Tong3Department of Thyroid Vascular Surgery, Jingzhou Central Hospital, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, 434000, China; Corresponding author. Department of Thyroid Vascular Surgery, Jingzhou Central Hospital, Jingzhou Hospital Affiliated to Yangtze University, No. 26, Chuyuan Avenue, Jingzhou District, Jingzhou, Hubei, 434000, China.Department of Oncology, Huanggang Central Hospital, Huanggang, 438000, ChinaDepartment of Dermatology, Jingzhou Central Hospital, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, 434000, ChinaDepartment of Thyroid Vascular Surgery, Jingzhou Central Hospital, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, 434000, ChinaThyroid 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.http://www.sciencedirect.com/science/article/pii/S0890850824000392Thyroid cancerMethyltransferase-like 14 (METTL14)N6-methyladenosine (m6A)Suppressor of cytokine signaling 3 (SOCS3) |
| spellingShingle | Ming Zhou Yaqi Zhang Qiong Zhang Yanchu Tong METTL14-mediated m6A modification upregulated SOCS3 expression alleviates thyroid cancer progression by regulating the JAK2/STAT3 pathway Molecular and Cellular Probes Thyroid cancer Methyltransferase-like 14 (METTL14) N6-methyladenosine (m6A) Suppressor of cytokine signaling 3 (SOCS3) |
| title | METTL14-mediated m6A modification upregulated SOCS3 expression alleviates thyroid cancer progression by regulating the JAK2/STAT3 pathway |
| title_full | METTL14-mediated m6A modification upregulated SOCS3 expression alleviates thyroid cancer progression by regulating the JAK2/STAT3 pathway |
| title_fullStr | METTL14-mediated m6A modification upregulated SOCS3 expression alleviates thyroid cancer progression by regulating the JAK2/STAT3 pathway |
| title_full_unstemmed | METTL14-mediated m6A modification upregulated SOCS3 expression alleviates thyroid cancer progression by regulating the JAK2/STAT3 pathway |
| title_short | METTL14-mediated m6A modification upregulated SOCS3 expression alleviates thyroid cancer progression by regulating the JAK2/STAT3 pathway |
| title_sort | mettl14 mediated m6a modification upregulated socs3 expression alleviates thyroid cancer progression by regulating the jak2 stat3 pathway |
| topic | Thyroid cancer Methyltransferase-like 14 (METTL14) N6-methyladenosine (m6A) Suppressor of cytokine signaling 3 (SOCS3) |
| url | http://www.sciencedirect.com/science/article/pii/S0890850824000392 |
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