The functions and prognostic values of m6A RNA methylation regulators in thyroid carcinoma.
TL;DR: Wang et al. as discussed by the authors used LASSO Cox regression analysis to generate a prognostic signature based on m6A RNA modification regulator expression and found that this risk signature could better predict outcome in male than female.
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Abstract: 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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FTO in cancer: functions, molecular mechanisms, and therapeutic implications.
TL;DR: In this article , the authors reviewed recent advances in understanding of the functions and underlying molecular mechanisms of FTO in tumor development, cancer stem cell (CSC) self-renewal, microenvironment regulation, immunity, and metabolism and discuss the therapeutic potential of targeting FTO for cancer treatment.
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TS-m6A-DL: Tissue-specific identification of N6-methyladenosine sites using a universal deep learning model.
TL;DR: Wang et al. as mentioned in this paper proposed a universal model using deep neural network (DNN) and named it TS-m6A-DL, which can classify m6A sites in several tissues of humans (Homo sapiens), mice (Mus musculus), and rats (Rattus norvegicus).
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METTL3 inhibition induced by M2 macrophage-derived extracellular vesicles drives anti-PD-1 therapy resistance via M6A-CD70-mediated immune suppression in thyroid cancer.
Junya Ning,Xiukun Hou,Jie Hao,Wei Zhang,Yi Shi,Yue Huang,Xianhui Ruan,Xiangqian Zheng,Ming Gao +8 more
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FTO promotes cervical cancer cell proliferation, colony formation, migration and invasion via the regulation of the BMP4/Hippo/YAP1/TAZ pathway.
TL;DR: In this article , the authors investigated the role of fat mass and obesity associated gene (FTO) in the development of cervical cancer and showed that the demethylase activity of FTO is required for cell proliferation, colony formation, migration, and invasion.
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Interpretable prediction models for widespread m6A RNA modification across cell lines and tissues.
Ying Zhang,Zhikang Wang,Yiwen Zhang,Shanshan Li,Yuming Guo,Jiangning Song,Dong-Jun Yu +6 more
TL;DR: CLM6A, a set of deep learning-based models designed for predicting single-nucleotide-resolution m6A RNA modification sites across eight different cell lines and three tissues, achieves superior performance than current state-of-the-art methods and exhibits better portability on similar cross-cell line/tissue datasets.
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N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO.
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TL;DR: FTO exhibits efficient oxidative demethylation activity of abundant N6-methyladenosine (m6A) residues in RNA in vitro, and it is shown that FTO partially colocalizes with nuclear speckles, supporting m6A in nuclear RNA as a physiological substrate of FTO.
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ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility
Guanqun Zheng,John Arne Dahl,Yamei Niu,Peter Fedorcsak,Chun-Min Huang,Charles J. Li,Cathrine Broberg Vågbø,Yue Shi,Yue Shi,Wen-Ling Wang,Wen-Ling Wang,Shuhui Song,Zhike Lu,Ralph P. G. Bosmans,Qing Dai,Ya-Juan Hao,Ya-Juan Hao,Xin Yang,Xin Yang,Wenming Zhao,Wei-Min Tong,Xiu-Jie Wang,Florian Bogdan,Kari Furu,Ye Fu,Guifang Jia,Xu Zhao,Xu Zhao,Jun Liu,Hans E. Krokan,Arne Klungland,Yun-Gui Yang,Yun-Gui Yang,Chuan He +33 more
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YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA.
Hailing Shi,Xiao Wang,Xiao Wang,Zhike Lu,Zhike Lu,Boxuan S Zhao,Boxuan S Zhao,Honghui Ma,Honghui Ma,Phillip J. Hsu,Phillip J. Hsu,Chang Liu,Chang Liu,Chuan He,Chuan He +14 more
TL;DR: All three YTHDF proteins may act in an integrated and cooperative manner to impact fundamental biological processes related to m6A RNA methylation in the cytoplasm.
FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N 6-Methyladenosine RNA Demethylase
Zejuan Li,Hengyou Weng,Hengyou Weng,Rui Su,Xiaocheng Weng,Xiaocheng Weng,Zhixiang Zuo,Zhixiang Zuo,Zhixiang Zuo,Chenying Li,Chenying Li,Huilin Huang,Sigrid Nachtergaele,Lei Dong,Chao Hu,Chao Hu,Chao Hu,Xi Qin,Lichuan Tang,Yungui Wang,Yungui Wang,Yungui Wang,Gia-Ming Hong,Hao Huang,Xiao Wang,Ping Chen,Sandeep Gurbuxani,Stephen Arnovitz,Yuanyuan Li,Shenglai Li,Jennifer Strong,Mary Beth Neilly,Richard A. Larson,Xi Jiang,Xi Jiang,Pumin Zhang,Jie Jin,Chuan He,Jianjun Chen,Jianjun Chen +39 more
TL;DR: It is shown that FTO, as an m6A demethylase, plays a critical oncogenic role in acute myeloid leukemia (AML) and provides profound insights into leukemogenesis and drug response.
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