METTL3-Induced miR-222-3p Upregulation Inhibits STK4 and Promotes the Malignant Behaviors of Thyroid Carcinoma Cells
| Autor: | Cheng-Cheng Ji, Cheng Zhang, Yue Zhu, Xinzhi Peng, Shaojian Lin, Langping Tan, Weiming Yu, Miaoyun Long, Dingyuan Luo |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty Adenosine Endocrinology Diabetes and Metabolism Clinical Biochemistry Thyroid Gland Down-Regulation Context (language use) Kaplan-Meier Estimate Protein Serine-Threonine Kinases Biochemistry Metastasis Thyroid carcinoma Mice Endocrinology Downregulation and upregulation Internal medicine Animals Humans Medicine Cytotoxic T cell Gene silencing Thyroid Neoplasms Aged Gene knockdown business.industry Biochemistry (medical) Intracellular Signaling Peptides and Proteins Methyltransferases Middle Aged medicine.disease Xenograft Model Antitumor Assays Up-Regulation MicroRNAs Cell Transformation Neoplastic Cell culture Gene Knockdown Techniques Thyroidectomy Cancer research Female business Follow-Up Studies |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 107:474-490 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/clinem/dgab480 |
| Popis: | Context Abnormally high expression of N6-methyladenosine (m6A) methyltransferase-like 3 (METTL3) has been implied to accompany thyroid carcinoma (TC) development. Objective This study aimed to explore the protumorigenic role and downstream signaling axis of METTL3 in TC. Methods This study was conducted at the Sun Yat-Sen Memorial Hospital Sun Yat-Sen University. METTL3 and miR-222-3p were overexpressed or downregulated in TC cells. Tumor and adjacent normal tissues were collected from 80 patients (19 men and 60 women, aged 30-70 years) with a pathological diagnosis of TC from January 2012 to January 2015. Cells were classified and subjected to different treatments. The expression of METTL3 was validated in TC tissues and cell lines. In functional studies, METTL3 and miR-222-3p were overexpressed or downregulated in TC cells to evaluate their effects on malignant behaviors, which were subsequently verified by xenografts in nude mice. Results The expression of METTL3 was elevated in TC, correlating with poor prognosis of TC patients. Heightened METTL3 expression accelerated malignant behaviors of TC cells. Mechanistically, METTL3 stimulated miR-222-3p expression by mediating the m6A modification of pri-miR-222-3p. miR-222-3p targeted and inversely regulated serine/threonine stress kinase 4 (STK4). Knockdown of METTL3 augmented STK4 expression by downregulating miR-222-3p, thereby suppressing the malignant behaviors of TC cells as well as tumor growth and lung metastasis in nude mice. Conclusion Silencing METTL3 suppresses miR-222-3p expression and thus stimulates STK4 expression, thereby repressing the malignancy and metastasis of TC. |
| Databáze: | OpenAIRE |
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