Emerging roles of RNA methylation in gastrointestinal cancers
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Cancer Cell International Open Access
REVIEW
Emerging roles of RNA methylation in gastrointestinal cancers Shanshan Xie1,2, Wenwen Chen2, Kanghua Chen2, Yongxia Chang2, Feng Yang2, Aifu Lin3, Qiang Shu1, Tianhua Zhou2,4* and Xiaoyi Yan2*
Abstract RNA methylation has emerged as a fundamental process in epigenetic regulation. Accumulating evidences indicate that RNA methylation is essential for many biological functions, and its dysregulation is associated with human cancer progression, particularly in gastrointestinal cancers. RNA methylation has a variety of biological properties, including N6-methyladenosine (m6A), 2-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C) and 7-methyl guanosine (m7G). Dynamic and reversible methylation on RNA is mediated by RNA modifying proteins called “writers” (methyltransferases) and “erasers” (demethylases). “Readers” (modified RNA binding proteins) recognize and bind to RNA methylation sites, which influence the splicing, stability or translation of modified RNAs. Herein, we summarize the biological functions and mechanisms of these well-known RNA methylations, especially focusing on the roles of m6A in gastrointestinal cancer development. Keywords: RNA methylation, m6A, m6Am, m1A, m5C, Gastrointestinal cancers Background Gastrointestinal (GI) cancers refer to malignant conditions of the GI tract and accessory organs of digestion including liver and pancreas. Globally, GI cancers account for roughly half of all cancer-related deaths [1, 2]. GI cancers have high mortality rates, mainly because of asymptomatic at early-stages, and limited treatment options and poor prognosis at advanced stages. Thus, the identification of robust biomarkers for early-stage and the development of new drugs to treat GI cancers are urgently needed. Even though modification events in RNA molecules were discovered in the 1950s, our understanding of RNA modification is limited [3–6]. Recently, with the rapid development of transcriptomics technologies, studies about the physiological and pathological function of RNA
*Correspondence: [email protected]; [email protected] 2 Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China Full list of author information is available at the end of the article
modification come to the forefront. To date, over 170 RNA modifications have been identified, including RNA methylation and pseudouridylation (Ψ). These modifications have been identified to distribute extensively in kinds of RNAs, such as messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs) [7]. Among RNA modifications, RNA methylation is the most well-characterized type. Highly dynamic and reversible methylation on RNA is mediated by a number of proteins, which are called RNA-modifying proteins (RMPs) [8, 9]. RMPs include “writers” and “erasers” that respectively decorate and remove methylations on RNA respectively, and ‘‘readers’’ that recognize and bind to the me
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