&lt;p&gt;Progression of Thyroid Carcinoma Is Promoted by the m6A Methyltransferase METTL3 Through Regulating m6A Methylation on TCF1&lt;/p&gt;

Wang, Kejin; Jiang, Lin; Zhang, Yan; Chen, Chao

doi:10.2147/ott.s234751

Cited by 31 publications

(24 citation statements)

References 33 publications

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“…Overexpression of IGF2BP2 has been indicated to be related to poor survival of patients with colorectal cancer, acute myelocytic leukemia and metaplastic breast cancer [30,31]. Recently, K.Wang et al demonstrated that the progression of thyroid carcinoma can be promoted by METTL3 and IGF2BP2 through m6A methylation on TCF1 mRNA and activation of Wnt signaling pathway in thyroid cancer [32]. The relationship between IGF2BP2 and PI3K/ Akt signaling pathway has been discussed, suggesting up-regulated IGF2BP2 in pancreatic cancer plays a role in cell proliferation [33].…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of m6A RNA methylation regulators with clinical prognostic value in Papillary thyroid cancer

Wang

Zhang

et al. 2020

Cancer Cell Int

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Background: Papillary thyroid cancer (PTC) is a type of malignant tumor with excellent prognosis, accounting for more than 80% of thyroid cancer. Recently, numerous studies illustrated the importance of N 6-methyladenosine (m 6 A) RNA modification to tumorigenesis, but it has never been reported in PTC. Methods: We downloaded data from The Cancer Genome Atlas (TCGA) and analyzed RNA expression, single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) of 19 m 6 A RNA methylation regulators in PTC. Then we used nonnegative matrix factorization (NMF) to cluster patients into two m 6 A subtypes and compared them in overall survival (OS) and disease-free survival (DFS). The Weighted correlation network analysis (WGCNA) and univariate Cox proportional hazard model (CoxPH) were used to select genes for the construction of a m 6 A-related signature. The accuracy and prognostic value of this signature were validated by using receiver operating characteristic (ROC) curves, K-M (Kaplan-Meier) survival analysis, univariant and multivariant analyses. Results: CNVs and differential expression of m 6 A regulators were observed in PTC patients. Especially IGF2BP2 (Insulin-like growth factor 2 mRNA binding protein 2), which was most significantly overexpressed in tumor tissue. We chose 4 genes in the m 6 A-related module from WGCNA: IGF2BP2, STT3A, MTHFD1 and GSTM4, and used them to construct a m 6 A-related signature. The prognostic value of this signature was validated, and risk scores provided by the signature was the independent prognostic factor for PTC. A nomogram was also provided for clinical usage. Conclusions: We performed a comprehensive evaluation of the m 6 A RNA modification landscape of PTC and explored its underlying mechanisms. Our m 6 A-related signature was of great significance in predicting the DFS of patients with PTC. And IGF2BP2 was a gene worthy for further analysis as its strong correlation with DFS and clinical phenotypes of PTC.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of m6A RNA methylation regulators with clinical prognostic value in Papillary thyroid cancer

Wang

Zhang

et al. 2020

Cancer Cell Int

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“…LEF1, ATAD2, c-Met, AKT, ΔNp63, and ZNF750 have been suggested as oncogenes in association with METTL3 with uncharacterized pathways [ 105 , 107 , 110 , 111 , 113 , 114 ]. Several mRNAs, including DRG1 , MYC , and TCF1 , as well as non-coding RNA lncAROD , have been suggested as METTL3 targets that are stabilized in a m 6 A-dependent manner, resulting in cell proliferation and/or migration in osteosarcoma, oral squamous cell carcinoma (OSCC), thyroid carcinoma, and head and neck squamous cell carcinoma (HNSCC), respectively [ 106 , 108 , 109 , 112 ]. It is noteworthy that in the case of OSCC, the authors concluded that the m 6 A modification in MYC enhanced the mRNA stability mediated by YTHDF1 [ 108 ], which was a different mechanism from that in other reports and highlighted the functional complexity of the protein.…”

Section: Mettl3 Functions As An M 6 a Methyltransfmentioning

confidence: 99%

Roles of METTL3 in cancer: mechanisms and therapeutic targeting

et al. 2020

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N 6-methyladenosine (m 6 A) is the most abundant mRNA modification and is catalyzed by the methyltransferase complex, in which methyltransferase-like 3 (METTL3) is the sole catalytic subunit. Accumulating evidence in recent years reveals that METTL3 plays key roles in a variety of cancer types, either dependent or independent on its m 6 A RNA methyltransferase activity. While the roles of m 6 A modifications in cancer have been extensively reviewed elsewhere, the critical functions of METTL3 in various types of cancer, as well as the potential targeting of METTL3 as cancer treatment, have not yet been highlighted. Here we summarize our current understanding both on the oncogenic and tumor-suppressive functions of METTL3, as well as the underlying molecular mechanisms. The welldocumented protein structure of the METTL3/METTL14 heterodimer provides the basis for potential therapeutic targeting, which is also discussed in this review.

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“…The studies were screened according to the following procedure [19,[39][40][41][42][43][44][45][46][47][48] (Fig. 1).At rst We retrieved a total of 349 articles from the online database.After preliminary screening and duplicate checking, 253 articles were retained.Through reading the title and abstract of the articles, the articles were further screened.Studies of 207 related to METTL3 expression and cancer prognosis were excluded according to exclusion criteria.…”

Section: Eligible Researchesmentioning

confidence: 99%

The prognostic value of METTL3 in cancer patients: a meta-analysis

Pan

et al. 2020

Preprint

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Background: M6A methylation modification of RNA can regulate the development of tumor cells. METTL3 is one of the modified methyltransferases. A growing number of studies have shown that high expression of METTL3 may be associated with the unfavorable prognosis in cancer patients and may become a new biomarker. Therefore, this meta-analysis was used to evaluate the prognostic value of METTL3 in cancer patients through the available literature information.Methods: Relevant studies were retrieved from electronic literature databases including six English databases and three Chinese databases. Correlation analysis was conducted by Stata SE 15.1 and RevMan 5.3 software. We analyzed 11 eligible studies with a total of 1638 cancer patients in this meta-analysis. We took advantage of HRs and ORs with 95% confidence intervals to evaluate the prognostic value of METTL3 in tumors. Besides,the article was qualified by MOOSE check lists and PRISMA Checklist. Results: The results of the meta-analysis indicated that high expression of METTL3 was associated with low overall survival (OS) (HR=2.67, 95%CI:2.19-3.25, P<0.00001) and disease-free survival (DFS) (HR=2.23, 95%CI:1.60-3.11, P<0.00001) in various cancers.Stratified analysis of cancer types showed that over expressed METTL3 was related to poor prognosis in digestive system cancer patients, including CRC(HR=2.29, 95%CI:1.50-3.49，P=0.0001) ,GC(HR=2.96，95%CI:2.13-4.12，P＜0.00001)，and liver cancer（HR=2.70，95%CI:1.88-3.88，P＜0.00001). Meanwhile, the elevated METTL3 expression also affected the lymph node metastasis (OR=3.40，95%CI=1.58-7.33，p=0.002) ，vascular invasion (OR=2.04，95%CI=1.06-3.95，p=0.03) and the tumors progression (III/IV vs. I/II: OR = 3.72, 95% CI: 1.94 - 7.13, P < 0.0001).Conclusion: The existing analysis indicates that METTL3 is associated with low OS and DFS in cancer patients and may serve as a biomarker to assess prognostic value.

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<p>Progression of Thyroid Carcinoma Is Promoted by the m6A Methyltransferase METTL3 Through Regulating m6A Methylation on TCF1</p>

Cited by 31 publications

References 33 publications

Identification and validation of m6A RNA methylation regulators with clinical prognostic value in Papillary thyroid cancer

Identification and validation of m6A RNA methylation regulators with clinical prognostic value in Papillary thyroid cancer

Roles of METTL3 in cancer: mechanisms and therapeutic targeting

The prognostic value of METTL3 in cancer patients: a meta-analysis

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