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      The role of RNA m 5C modification in cancer metastasis

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          Abstract

          Epigenetic modification plays a crucial regulatory role in the biological processes of eukaryotic cells. The recent characterization of DNA and RNA methylation is still ongoing. Tumor metastasis has long been an unconquerable feature in the fight against cancer. As an inevitable component of the epigenetic regulatory network, 5-methylcytosine is associated with multifarious cellular processes and systemic diseases, including cell migration and cancer metastasis. Recently, gratifying progress has been achieved in determining the molecular interactions between m 5C writers (DNMTs and NSUNs), demethylases (TETs), readers (YTHDF2, ALYREF and YBX1) and RNAs. However, the underlying mechanism of RNA m 5C methylation in cell mobility and metastasis remains unclear. The functions of m 5C writers and readers are believed to regulate gene expression at the post-transcription level and are involved in cellular metabolism and movement. In this review, we emphatically summarize the recent updates on m 5C components and related regulatory networks. The content will be focused on writers and readers of the RNA m 5C modification and potential mechanisms in diseases. We will discuss relevant upstream and downstream interacting molecules and their associations with cell migration and metastasis.

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          Most cited references137

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          Dynamic RNA Modifications in Gene Expression Regulation

          Over 100 types of chemical modifications have been identified in cellular RNAs. While the 5' cap modification and the poly(A) tail of eukaryotic mRNA play key roles in regulation, internal modifications are gaining attention for their roles in mRNA metabolism. The most abundant internal mRNA modification is N6-methyladenosine (m6A), and identification of proteins that install, recognize, and remove this and other marks have revealed roles for mRNA modification in nearly every aspect of the mRNA life cycle, as well as in various cellular, developmental, and disease processes. Abundant noncoding RNAs such as tRNAs, rRNAs, and spliceosomal RNAs are also heavily modified and depend on the modifications for their biogenesis and function. Our understanding of the biological contributions of these different chemical modifications is beginning to take shape, but it's clear that in both coding and noncoding RNAs, dynamic modifications represent a new layer of control of genetic information.
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            The diverse roles of DNA methylation in mammalian development and disease

            DNA methylation is of paramount importance for mammalian embryonic development. DNA methylation has numerous functions: it is implicated in the repression of transposons and genes, but is also associated with actively transcribed gene bodies and, in some cases, with gene activation per se. In recent years, sensitive technologies have been developed that allow the interrogation of DNA methylation patterns from a small number of cells. The use of these technologies has greatly improved our knowledge of DNA methylation dynamics and heterogeneity in embryos and in specific tissues. Combined with genetic analyses, it is increasingly apparent that regulation of DNA methylation erasure and (re-)establishment varies considerably between different developmental stages. In this Review, we discuss the mechanisms and functions of DNA methylation and demethylation in both mice and humans at CpG-rich promoters, gene bodies and transposable elements. We highlight the dynamic erasure and re-establishment of DNA methylation in embryonic, germline and somatic cell development. Finally, we provide insights into DNA methylation gained from studying genetic diseases.
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              MODOMICS: a database of RNA modification pathways. 2017 update

              Abstract MODOMICS is a database of RNA modifications that provides comprehensive information concerning the chemical structures of modified ribonucleosides, their biosynthetic pathways, the location of modified residues in RNA sequences, and RNA-modifying enzymes. In the current database version, we included the following new features and data: extended mass spectrometry and liquid chromatography data for modified nucleosides; links between human tRNA sequences and MINTbase - a framework for the interactive exploration of mitochondrial and nuclear tRNA fragments; new, machine-friendly system of unified abbreviations for modified nucleoside names; sets of modified tRNA sequences for two bacterial species, updated collection of mammalian tRNA modifications, 19 newly identified modified ribonucleosides and 66 functionally characterized proteins involved in RNA modification. Data from MODOMICS have been linked to the RNAcentral database of RNA sequences. MODOMICS is available at http://modomics.genesilico.pl.
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                Author and article information

                Journal
                Int J Biol Sci
                Int J Biol Sci
                ijbs
                International Journal of Biological Sciences
                Ivyspring International Publisher (Sydney )
                1449-2288
                2021
                2 August 2021
                : 17
                : 13
                : 3369-3380
                Affiliations
                [1 ]Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
                [2 ]Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Wuhan, Hubei 430030, China.
                [3 ]Hubei key laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
                Author notes
                ✉ Corresponding authors: Prof. Zhanguo Zhang, or Bixiang Zhang; Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, 1095 Jiefang Avenue, 430030 Wuhan, China. Tel.: +86 27 83663400; fax: +86 27 83662851; E-mail: zhanguo_tjh@ 123456hust.edu.cn , bixiangzhang@ 123456163.com

                † Qiaofeng Zhang and Furong Liu contributed equally to this work.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                ijbsv17p3369
                10.7150/ijbs.61439
                8416729
                34512153
                a194a584-a6f4-40da-92ed-8671bba1c49f
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 17 June 2021
                : 19 July 2021
                Categories
                Review

                Life sciences
                metastasis,cell migration,5-methylcytosine,ribosome acid,regulatory network
                Life sciences
                metastasis, cell migration, 5-methylcytosine, ribosome acid, regulatory network

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