The Role of m6A Modification and m6A Regulators in Esophageal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. m6A Modification and m6A Regulators
2.1. Methyltransferases
2.2. Demethylases
2.3. m6A RNA Binding Proteins
3. m6A Modification and Its Effect on Various RNAs in ESCA
3.1. m6A Modification in ESCA
3.2. The Effect of m6A Modification on mRNA in ESCA
3.3. The Effect of m6A Modification on Non-Coding RNAs in ESCA
4. The Role of m6A Regulators in Development, Progression, Prognosis and Treatment of ESCA
4.1. m6A Regulators and EAC
4.2. m6A Regulators and ESCA (Not including EAC)
4.2.1. The Expression of m6A Regulators and their Association with Clinicopathological Characteristic in ESCA
- Writers
- Erasers
- Readers
4.2.2. The Effect and Mechanism of m6A Regulators in Progression of ESCA
m6A Regulators Regulated Biological Behavior of ESCC Cells in an m6A-Dependent Way
- Writers
- Erasers
- Readers
m6A Regulators Regulated Biological Behavior of ESCC Cells in an m6A-Independent Way
- Writers
- Erasers
- Readers
- Combined Effects of m6A Regulators in Progression of ESCA
4.2.3. The Role of m6A Regulators in Treatment of ESCA
4.2.4. The Association between Expression of m6A Regulators and Prognosis of ESCA Patients
5. Conclusions and Perspectives
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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m6A Regulator | Target | Type of Target RNA | Function | Molecular Mechanism | Reference |
---|---|---|---|---|---|
METTL3 | GLS2 | mRNA | Writer | Increase m6A level of GLS2 mRNA, upregulate GLS2 expression | [59] |
METTL3 | NOTCH1 | mRNA | Writer | Increase m6A level of NOTCH1 mRNA, upregulate NOTCH1 expression | [60] |
METTL3 | TNFR1 | mRNA | Writer | Increase m6A level of TNFR1 mRNA, upregulate TNFR1 expression | [61] |
ALKBH5 | CDKN1A | mRNA | Eraser | Decrease m6A level of CDKN1A mRNA, decrease stability of CDKN1A mRNA, downregulate p21 expression | [62] |
FTO | SIM2 | mRNA | Eraser | Decrease m6A level of SIM2 mRNA, decrease stability of SIM2 mRNA, downregulate SIM2 expression | [63] |
IGF2BP2 | CTNNB1 | mRNA | Reader | Increase stability of CTNNB1 mRNA, upregulate CTNNB1 expression | [64] |
IGF2BP2 | FOXP4 | mRNA | Reader | Increase stability of FOXP4 mRNA, upregulate FOXP4 expression | [65] |
IGF2BP2 | TK1 | mRNA | Reader | Recognize m6A of TK1 mRNA, upregulate TK1 expression | [66] |
IGF2BP2 | KIF18A | mRNA | Reader | Increase stability of KIF18A mRNA, upregulate expression of KIF18A | [67] |
HNRNPC | ZEB1 and ZEB2 | mRNA | Reader | Increase stability of ZEB1 and ZEB2 mRNA, upregulate expression of ZEB1 and ZEB2 | [68] |
METTL3, METTL14, and YTHDF2 | APC | mRNA | METTL3 and METTL14 as writer; YTHDF2 as reader | METTL3 increases m6A level of APC mRNA in an METTL14-dependent way; YTHDF2 promotes degradation of APC mRNA | [69] |
IGF2BP2 and IGF2BP3 | HTR3A | mRNA | Reader | Increase stability of HTR3A mRNA, upregulate HTR3A expression | [70] |
METTL3 and YTHDF1 | HK2 | mRNA | METTL3 as writer; YTHDF1 as reader | Increase stability of HK2 mRNA, upregulate HK2 expression | [71] |
METTL3 and YTHDF3 | EGR1 | mRNA | METTL3 as writer; YTHDF3 as reader | Increase stability of EGR1 mRNA, upregulate EGR1 expression | [72] |
FTO and YTHDF1 | ERBB2 | mRNA | FTO as eraser; YTHDF1 as reader | Increase stability of ERBB2 mRNA, upregulate ERBB2 expression | [73] |
FTO and YTHDF1 | HSD17B11 | mRNA | FTO as eraser; YTHDF1 as reader | Decrease the translation efficiency of HSD17B11 mRNA, downregulate HSD17B11 expression | [74] |
METTL3 | pri-miR-200-5p | miRNA | Writer | Increase m6A level of pri-miR-200-5p, upregulate miR-200-5p expression | [75] |
METTL3 | pri-miR-320b | miRNA | Writer | Increase m6A level of pri-miR-320b, upregulate miR-320b expression | [76] |
METTL14 | pri-miR-99a | miRNA | Writer | Increase m6A level of pri-miR-99a, upregulate miR-99a-5p expression | [77] |
ALKBH5 | pri-miR-194-2 | miRNA | Eraser | Decrease m6A level of pri-miR-194-2, downregulate miR-194-2 expression | [78] |
HNRNPA2B1 | miR-17-92 cluster | miRNA | Reader | Bind to m6A of miR-17-92 cluster, upregulate expression of miR-17-92 cluster | [79] |
METTL3 and ALKBH5 | pri-miR-193a-3p | miRNA | METTL3 as writer; ALKBH5 as eraser | METTL3 increases m6A level of pri-miR-193a-3p, upregulates miR-193a-3p expression; ALKBH5 decreases m6A level of pri-miR-193a-3p, downregulates miR-193a-3p expression | [80] |
METTL3, METTL14, WTAP, ALKBH5, and YTHDF1 | LINC00278 | lncRNA | METTL3, METTL14, and WTAP as writers; ALKBH5 as eraser; YTHDF1 as reader | METTL3, METTL14, and WTAP increase m6A level of LINC00278; ALKBH5 decreases m6A level of LINC00278; YTHDF1 promotes translation of LINC00278 | [81] |
METTL3, RBM15, WTAP, and YTHDC2 | MALAT1 | lncRNA | METTL3, RBM15, and WTAP as writer; YTHDC2 as reader | RBM15 interacts with METTL3 in a WTAP-dependent way to deposit m6A onto MALAT1; YTHDC1 binds to m6A of MALAT1 and maintains composition of nuclear speckle | [82] |
FTO and YTHDF2 | LINC00022 | lncRNA | FTO as eraser; YTHDF2 as reader | FTO reduces the enrichment of m6A at site 2 of LINC00022 transcript; YTHDF2 promotes degradation of LINC00022 | [83] |
m6A Regulator | Upstream Gene | Type of Upstream Gene | Molecular Mechanism | Reference |
---|---|---|---|---|
METTL3 | SNHG3 and miR-186-5p | lncRNA and miRNA | SNHG3 sponges miR-186-5p and alleviates inhibition of METTL3 by miR-186-5p | [122] |
WTAP | EMS and miR-758-3p | lncRNA and miRNA | EMS sponges miR-758-3p and alleviates inhibition of METTL3 by miR-758-3p | [129] |
IGF2BP2 | CCAT2 and miR-200b | lncRNA and miRNA | CCAT2 sponges miR-200b and alleviates inhibition of IGF2BP2 by miR-200b | [66] |
IGF2BP1 | miR-454-3p | miRNA | miR-454-3p inhibits expression of IGF2BP1 | [135] |
HNRNPC | miR-186 | miRNA | miR-186 inhibits expression of HNRNPC | [136] |
ALKBH5 | miR-193a-3p | miRNA | miR-193a-3p inhibits expression of ALKBH5 | [80] |
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Li, Y.; Niu, C.; Wang, N.; Huang, X.; Cao, S.; Cui, S.; Chen, T.; Huo, X.; Zhou, R. The Role of m6A Modification and m6A Regulators in Esophageal Cancer. Cancers 2022, 14, 5139. https://doi.org/10.3390/cancers14205139
Li Y, Niu C, Wang N, Huang X, Cao S, Cui S, Chen T, Huo X, Zhou R. The Role of m6A Modification and m6A Regulators in Esophageal Cancer. Cancers. 2022; 14(20):5139. https://doi.org/10.3390/cancers14205139
Chicago/Turabian StyleLi, Yuekao, Chaoxu Niu, Na Wang, Xi Huang, Shiru Cao, Saijin Cui, Tianyu Chen, Xiangran Huo, and Rongmiao Zhou. 2022. "The Role of m6A Modification and m6A Regulators in Esophageal Cancer" Cancers 14, no. 20: 5139. https://doi.org/10.3390/cancers14205139