<p>Progression of Thyroid Carcinoma Is Promoted by the m6A Methyltransferase METTL3 Through Regulating m6A Methylation on TCF1</p>
Authors: Lin Jiang
Chao Chen
Yan Zhang
Kejin Wang
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: TCF1; m6A; methyltransferase METTL3; migration; thyroid carcinoma.
Affiliations: 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 China.

Abstract:  Objective: 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. 

Retracted: No

PubPeer comments:
 This paper is one of a set of (as of now) six papers that share unexpected similarities. The papers are from different groups of authors at different hospitals, describing different cancer types. Yet, they share several similar features. * All six papers describe a group of 48 patients * Five of the six papers describe the same set of GAPDH primers. One of them (the RV primer) does not appear to match the GAPDH mRNA sequence. This particular paper, however, does not list any primer sequences. * Figures 1 of all papers show black bar graphs with error bars and a Kaplan-Meier curve with a blue and a red line * Three papers (XX Ma et al., JL Xu et al., K Wang et al.) share nearly identical positive correlation curves * All papers show photos of wound healing (scratch) assays with the same background, suggesting they were all taken with the same microscope. Here is the set of papers: * J.-L. Xu, T. Hua, J. Ding, Y. Fan, Z.-J. Liu, J.-W. Lian - FOXF2 aggravates the progression of non-small cell lung cancer through targeting lncRNA H19 to downregulate PTEN - Eur Rev Med Pharmacol Sci 2019; 23 (24): 10796-10802 - DOI: 10.26355 eurrev_201912_19782 - Department of Oncology, Xi an Chest Hospital, Xi an, China - https: pubpeer.com publications 8FC5B0039E9D0DF19B11FA3D02FE20 * Q.-Z. Meng, C.-H. Cong, X.-J. Li, F. Zhu, X. Zhao, F.-W. Chen - METTL3 promotes the progression of nasopharyngeal carcinoma through mediating M6A modification of EZH2 - Eur Rev Med Pharmacol Sci 2020; 24 (8): 4328-4336 - DOI: 10.26355 eurrev_202004_21014 - Department of Head and Neck Surgery, Linyi Cancer Hospital, Linyi, China - https: pubpeer.com publications 20860FD371C187E0260EB03EDED65E * T. Chen, J. Li, M.-H. Zhou, L.-J. Xu, T.-C. Pan - IL-6 stimulates lncRNA ZEB2-AS1 to aggravate the progression of non-small cell lung cancer through activating STAT1 - Eur Rev Med Pharmacol Sci 2020; 24 (7): 3734-3740 - DOI: 10.26355 eurrev_202004_20837 - Department of Cardiovascular Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China - https: pubpeer.com publications 3394043AD9D651B04C67F8130B6A5B * T. Zhou, J.-J. Fang, Y.-X. Zhou, Z.-P. Li, L. Jiang, W.-W. Han, Z.-H. Zhu - Long non-coding RNA ANCR promotes progression of NSCLC by inhibiting E-Ca expression - Eur Rev Med Pharmacol Sci 2020; 24 (3): 1250-1257 - DOI: 10.26355 eurrev_202002_20178 - Department of Respiratory Medicine, Zhoushan Hospital of Zhejiang University, Zhoushan, China - https: pubpeer.com publications 883758C5749162D81D41878BE99CBE (now retracted) * X.-X. Ma, Z.-G. Cao, S.-L. Zhao - m6A methyltransferase METTL3 promotes the progression of prostate cancer via m6A-modified LEF1 - Eur Rev Med Pharmacol Sci 2020; 24 (7): 3565-3571 - DOI: 10.26355 eurrev_202004_20817 - Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China - https: pubpeer.com publications 4721D50DF9998AC4A7577BFB0100CD * Kejin Wang, Lin Jiang , Yan Zhang , Chao Chen - Progression of Thyroid Carcinoma Is Promoted by the m6A Methyltransferase METTL3 Through Regulating m6A Methylation on TCF1 - OncoTargets and Therapy 2020:13 1605u20131612 - DOI: 10.2147 ott.s23475110.2147 ott.s234751 - 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, China - https: pubpeer.com publications 306C3260F8740491EA6BB799A2EC68 (this paper) Here is a comparison of the Figures 1 from three of these papers. The very similar looking correlation curves of XX Ma et al., JL Xu et al., and Kejin Wang et al. (this paper) have been highlighted with red boxes. ![file] ,