M6A Demethylase FTO Plays a Tumor Suppressor Role in Thyroid Cancer

Tian, Run; Zhang, Shidong; Sun, Da-Xin; Bei, Chunhua; Li, Di; Zheng, Chuanjun; Song, Xin; Chen, Mengshi; Tan, Shengkui; Zhu, Xiaonian; Zhang, Huixia

doi:10.1089/dna.2020.5956

Cited by 26 publications

(17 citation statements)

References 32 publications

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“…In cervical cancer, FTO enhances the chemoradiotherapy-resistance by reducing the m6A modification of β-catenin [ 29 ]. Recently, bioinformatic analysis has shown that FTO acts as anti-oncogene in thyroid cancer [ 30 ]. KIAA1429, known as VIRMA, mainly regulates the m6A mRNA methylation in 3′ UTR and near stop codon [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

The functions and prognostic values of m6A RNA methylation regulators in thyroid carcinoma

Feng

Zhang

et al. 2021

Cancer Cell Int

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Background N6-Methyladenosine (m6A) is the most common RNA modification and regulates RNA splicing, translation, translocation, and stability. Aberrant expression of m6A has been reported in various types of human cancers. m6A RNA modification is dynamically and reversibly mediated by different regulators, including methyltransferase, demethylases, and m6A binding proteins. However, the role of m6A RNA methylation regulators in thyroid cancer remains unknown. The aim of this study is to investigate the effect of the 13 main m6A RNA modification regulators in thyroid carcinoma. Methods We obtained clinical data and RNA sequencing data of 13 m6A RNA methylation regulators from The Cancer Genome Atlas (TCGA) THCA database. We performed consensus clustering to identify the clinical relevance of m6A RNA methylation regulators in thyroid carcinoma. Then we used LASSO Cox regression analysis to generate a prognostic signature based on m6A RNA modification regulator expression. Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Gene Set Enrichment Analyses were performed to explore differential cellular processes and signaling pathways between the two groups based on risk signature. Results We found that most of the m6A RNA modification regulators are down-regulated in 450 patients with thyroid carcinoma. We derived a three m6A RNA modification regulator genes-based risk signature (FTO, RBM15 and KIAA1429), that is an independent prognostic biomarker in patients with thyroid carcinoma. Moreover, we found that this risk signature could better predict outcome in male than female. Functional research in vitro demonstrated that the m6A RNA methylation regulators involved in the model acted significant role in the proliferation and migration of thyroid cancer cells. Conclusions Our study revealed the influence of m6A RNA methylation regulators on thyroid carcinoma through biological experiments and three-gene prognostic model.

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Section: Discussionmentioning

confidence: 99%

The functions and prognostic values of m6A RNA methylation regulators in thyroid carcinoma

Feng

Zhang

et al. 2021

Cancer Cell Int

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“…Reduced FTO nuclear expression has been reported to be associated with poor prognosis in human hepatocellular carcinoma [ 39 ]. FTO expression is downregulated in thyroid cancer tissues, which is associated with lymph node metastasis in thyroid cancer patients [ 40 ]. However, FTO also has a role in promoting cancer.…”

Section: Discussionmentioning

confidence: 99%

Potential role of m6A RNA methylation regulators in osteosarcoma and its clinical prognostic value

Liu¹,

Qin²,

et al. 2021

J Orthop Surg Res

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Background Osteosarcoma is a disease with high mortality in children and adolescents, and metastasis is one of the important clinical features of osteosarcoma. N6-Methyladenosine (m6A) is the most abundant methylation modification in mRNA, which is regulated by m6A regulators. It is reported that it is related to the occurrence and development of tumors. However, the mechanism of its action in osteosarcoma is rarely known. The purpose of this study was to identify the potential role of m6A regulatory factor in osteosarcoma and its clinical prognostic value. Methods Here, we used The Cancer Genome Atlas (TCGA) to comprehensively analyze the relationship between m6A regulatory factors and osteosarcoma (metastasis group and non-metastasis group). We analyzed their survival relationship and analyzed all the m6A regulatory factors in TCGA tumor data set by using the univariate Cox proportional hazard regression model. Finally, we selected two survival-related methylation regulators (FTO and IGF2BP2) as risk gene signature. Results According to the median risk, patients were divided into low-risk group and high-risk group. Multivariate Cox regression analysis showed that these two risk genes were considered to be the key factors independently predicting the prognosis of patients with osteosarcoma. In addition, we verified their characteristics with gene expression omnibus (GEO) DataSets and confirmed that they are related to tumor and immune-related signaling pathways through gene set enrichment analysis (GESA) and immune infiltration analysis. Conclusions In conclusion, m6A regulators might play an important role in the metastasis of osteosarcoma and have potential important value for the prognosis and treatment strategy of osteosarcoma patients.

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“…Based on these results, researchers preliminarily proved that the methylation process of m 6 A was reversibly and dynamically regulated. Previous studies have shown that the expression of the FTO gene was associated with breast cancer ( 41 ), thyroid cancer ( 43 ), endometrial cancer ( 44 ), gastric cancer ( 45 ), and other types of cancer ( 46 , 47 ). Li et al ( 48 ) found that FTO increased leukemia oncogene-mediated cell transformation and leukemogenesis by reducing the m 6 A modification of ASB2 and RARA genes, which led to the inhibition of AML cell differentiation induced by all-trans retinoic acid.…”

Section: Composition and Function Of M 6 A Modified Enzymementioning

confidence: 99%

Research progress concerning m⁶A methylation and cancer (Review)

et al. 2021

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N6-methyladenosine (m 6 A) methylation is a type of methylation modification on RNA molecules, which was first discovered in 1974, and has become a hot topic in life science in recent years. m 6 A modification is an epigenetic regulation similar to DNA and histone modification and is dynamically reversible in mammalian cells. This chemical marker of RNA is produced by m 6 A 'writers' (methylase) and can be degraded by m 6 A 'erasers' (demethylase). Methylated reading protein is the 'reader', that can recognize the mRNA containing m 6 A and regulate the expression of downstream genes accordingly. m 6 A methylation is involved in all stages of the RNA life cycle, including RNA processing, nuclear export, translation and regulation of RNA degradation, indicating that m 6 A plays a crucial role in RNA metabolism. Recent studies have shown that m 6 A modification is a complicated regulatory network in different cell lines, tissues and spatio-temporal models, and m 6 A methylation is associated with the occurrence and development of tumors. The present review describes the regulatory mechanism and physiological functions of m 6 A methylation, and its research progress in several types of human tumor, to provide novel approaches for early diagnosis and targeted treatment of cancer.

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M6A Demethylase FTO Plays a Tumor Suppressor Role in Thyroid Cancer

Cited by 26 publications

References 32 publications

The functions and prognostic values of m6A RNA methylation regulators in thyroid carcinoma

The functions and prognostic values of m6A RNA methylation regulators in thyroid carcinoma

Potential role of m6A RNA methylation regulators in osteosarcoma and its clinical prognostic value

Research progress concerning m⁶A methylation and cancer (Review)

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M6A Demethylase FTO Plays a Tumor Suppressor Role in Thyroid Cancer

Cited by 26 publications

References 32 publications

The functions and prognostic values of m6A RNA methylation regulators in thyroid carcinoma

The functions and prognostic values of m6A RNA methylation regulators in thyroid carcinoma

Potential role of m6A RNA methylation regulators in osteosarcoma and its clinical prognostic value

Research progress concerning m6A methylation and cancer (Review)

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Product

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Research progress concerning m⁶A methylation and cancer (Review)