OncoTargets and Therapy (Feb 2020)
Progression of Thyroid Carcinoma Is Promoted by the m6A Methyltransferase METTL3 Through Regulating m6A Methylation on TCF1
Abstract
Kejin Wang, Lin Jiang, Yan Zhang, Chao Chen Department of Head and Neck Surgery, Cancer Hospital of University of Chinese Academy of Sciences, Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Hangzhou, People’s Republic of ChinaCorrespondence: Chao ChenDepartment of Head and Neck Surgery, Cancer Hospital of University of Chinese Academy of Sciences, Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, No. 1, Banshan East Road, Hangzhou 310022, People’s Republic of ChinaTel +86 571 8812 2222Email [email protected]: This study aims to uncover the progression of thyroid carcinoma influenced by the m6A methyltransferase METTL3 through regulating m6A methylation on TCF1 mRNA and the activated Wnt pathway.Methods: Thyroid carcinoma tissues and paracancerous ones were collected for detecting levels of METTL3 and TCF1. Potential correlation between levels of METTL3 and TCF1 was analyzed by Pearson analysis. Survival of thyroid carcinoma patients influenced by METTL3 level was assessed by Kaplan–Meier method. Regulatory effect of METTL3 on migratory ability in TPC-1 cells was examined by wound healing assay. The interaction between METTL3 with TCF1 and IGF2BP2 was verified by RNA-Binding Protein Immunoprecipitation (RIP) assay. Meanwhile, the activity of the Wnt pathway was reflected by TOP/FOP-Flash. At last, rescue experiments were conducted to clarify the involvement of TCF1 in phenotype changes of thyroid carcinoma cells that were regulated by METTL3.Results: METTL3 and TCF1 were upregulated in thyroid carcinoma. Similarly, METTL3 was highly expressed in thyroid carcinoma cells as well. Kaplan–Meier method uncovered poor prognosis in thyroid carcinoma patients expressing a high level of METTL3. Silence of METTL3 inhibited migratory ability and Wnt activity in TPC-1 cells. RIP assay confirmed the interaction between TCF1 and METTL3 or IGF2BP2. Moreover, METTL3 positively regulated the enrichment abundance of TCF1 in anti-IGF2BP2. Rescue experiments demonstrated that TCF1 was responsible for METTL3-regulated thyroid carcinoma progression via the m6A methylation.Conclusion: Upregulated m6A methyltransferase METTL3 promotes the progression of thyroid carcinoma through m6A methylation on TCF1.Keywords: thyroid carcinoma, m6A, methyltransferase METTL3, TCF1, migration
