Advances in the role of m 6 A RNA modification in cancer metabolic reprogramming
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(2020) 10:117 Han et al. Cell Biosci https://doi.org/10.1186/s13578-020-00479-z
Open Access
REVIEW
Advances in the role of m6A RNA modification in cancer metabolic reprogramming Xiu Han, Lin Wang* and Qingzhen Han*
Abstract N6-methyladenosine (m6A) modification is the most common internal modification of eukaryotic mRNA and is widely involved in many cellular processes, such as RNA transcription, splicing, nuclear transport, degradation, and translation. m6A has been shown to plays important roles in the initiation and progression of various cancers. The altered metabolic programming of cancer cells promotes their cell-autonomous proliferation and survival, leading to an indispensable hallmark of cancers. Accumulating evidence has demonstrated that this epigenetic modification exerts extensive effects on the cancer metabolic network by either directly regulating the expression of metabolic genes or modulating metabolism-associated signaling pathways. In this review, we summarized the regulatory mechanisms and biological functions of m6A and its role in cancer metabolic reprogramming. Keywords: N6-methyladenosine, Detection techniques, Cancer metabolic reprogramming, Glycolysis Introduction N6-methyladenosine (m6A) is the most prevalent type of RNA modification of eukaryotic mRNAs [1, 2] and plays an important role in many biological functions including tissue development [3], naive pluripotency and stem cell differentiation [4], the heat shock response [5] and DNA damage [6]. m6A has been increasingly implicated in various human diseases such as obesity [7], diabetes [8], infertility [9], metabolic syndrome, and cancers [10–12]. In various cancers, m 6A functions as a promoter or suppressor in cancers by regulating the expression of cancer-related genes, which may affect the initiation [13], proliferation [14], differentiation [15], metastasis [16] and metabolic reprogramming of cancer cells [17]. In 2011, He et al. discovered that fat mass and obesity-associated protein (FTO) exhibited efficient demethylation of m6A residues in RNA in vitro [18]. Based on the finding that the internal amino acid sequence of FTO was similar to *Correspondence: [email protected]; [email protected] Center of Clinical Laboratory, Suzhou Dushu Lake Public Hospital, 9#, Chongwen Road, Suzhou 215000, People’s Republic of China
the active domains of DNA demethylases, a second m6A demethylase, Alk B homolog 5 (ALKBH5), was identified and confirmed [19]. Since then, major insights into the biological functions and regulatory mechanisms of m6A have been reported. Although FTO was found to be more active on N6,2′-O-dimethyladenosine (m6Am; at the cap + 1 position) than on m6A in internal mRNA in experiments [20], the FTO-mediated demethylation events that act on internal m6A are more important. This finding is because the fact that total cap m6Am level is less than 1/20 of that of the internal m6A, and approximately 95% of the observed m6A increases occurred on internal sites when FTO was knocked down in AML cells. More
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