The Role of M6A RNA Methylation in Cancer: Implication for Nature Products Anti-Cancer Research

Overview

Journal Front Pharmacol

Date 2022 Jul 5

PMID 35784761

Authors

Na Song

Kai Cui

Ke Zhang

Jie Yang

Jia Liu

Zhuang Miao

Feiyue Zhao

Hongjing Meng

Lu Chen

Chong Chen

Yushan Li

Minglong Shao

Jinghang Zhang

Haijun Wang

Affiliations

Soon will be listed here.

Abstract

N6-methyladenosine (m6A) RNA methylation is identified as the most common, abundant and reversible RNA epigenetic modification in messenger RNA (mRNA) and non-coding RNA, especially within eukaryotic messenger RNAs (mRNAs), which post-transcriptionally directs many important processes of RNA. It has also been demonstrated that m6A modification plays a pivotal role in the occurrence and development of tumors by regulating RNA splicing, localization, translation, stabilization and decay. Growing number of studies have indicated that natural products have outstanding anti-cancer effects of their unique advantages of high efficiency and minimal side effects. However, at present, there are very few research articles to study and explore the relationship between natural products and m6A RNA modification in tumorigenesis. m6A is dynamically deposited, removed, and recognized by m6A methyltransferases (METTL3/14, METTL16, WTAP, RBM15/15B, VIRMA, CBLL1, and ZC3H13, called as "writers"), demethylases (FTO and ALKBH5, called as "erasers"), and m6A-specific binding proteins (YTHDF1/2/3, YTHDC1/2, IGH2BP1/2/3, hnRNPs, eIF3, and FMR1, called as "readers"), respectively. In this review, we summarize the biological function of m6A modification, the role of m6A and the related signaling pathway in cancer, such as AKT, NF-kB, MAPK, ERK, Wnt/β-catenin, STAT, p53, Notch signaling pathway, and so on. Furthermore, we reviewed the current research on nature products in anti-tumor, and further to get a better understanding of the anti-tumor mechanism, thus provide an implication for nature products with anti-cancer research by regulating m6A modification in the future.

Citing Articles

RNA Modification in Metabolism.

Liu Y, Sun Z, Gui D, Zhao Y, Xu Y MedComm (2020). 2025; 6(3):e70135.

PMID: 40066222 PMC: 11892166. DOI: 10.1002/mco2.70135.

Beyond destruction: emerging roles of the E3 ubiquitin ligase Hakai.

Escuder-Rodriguez J, Rodriguez-Alonso A, Jove L, Quiroga M, Alfonsin G, Figueroa A Cell Mol Biol Lett. 2025; 30(1):9.

PMID: 39833727 PMC: 11749156. DOI: 10.1186/s11658-025-00693-y.

Targeting DTX2/UFD1-mediated FTO degradation to regulate antitumor immunity.

Cui Y, Wei J, Fan H, Li W, Zhao L, Wilkinson E Proc Natl Acad Sci U S A. 2024; 121(51):e2407910121.

PMID: 39661064 PMC: 11665913. DOI: 10.1073/pnas.2407910121.

ZC3H13 promotes autophagy in bladder cancer through m6A methylation modification of PJA2 and ubiquitination of KSR1.

Liu B, Chen M, Liang Y, Mei Z, Sun W, Gao W Hum Cell. 2024; 38(1):23.

PMID: 39614918 DOI: 10.1007/s13577-024-01155-x.

Modulation of host N6-methyladenosine modification by gut microbiota in colorectal cancer.

Jiang T, Wang H, Cheng W, Xie C World J Gastroenterol. 2024; 30(38):4175-4193.

PMID: 39493326 PMC: 11525875. DOI: 10.3748/wjg.v30.i38.4175.

References

Aboushanab S, Khedr S, Gette I, Danilova I, Kolberg N, Ravishankar G . Isoflavones derived from plant raw materials: bioavailability, anti-cancer, anti-aging potentials, and microbiome modulation. Crit Rev Food Sci Nutr. 2021; 63(2):261-287. DOI: 10.1080/10408398.2021.1946006. View

Onitsuka T, Uramoto H, Nose N, Takenoyama M, Hanagiri T, Sugio K . Acquired resistance to gefitinib: the contribution of mechanisms other than the T790M, MET, and HGF status. Lung Cancer. 2009; 68(2):198-203. DOI: 10.1016/j.lungcan.2009.05.022. View

Park S, Bazer F, Lim W, Song G . The O-methylated isoflavone, formononetin, inhibits human ovarian cancer cell proliferation by sub G0/G1 cell phase arrest through PI3K/AKT and ERK1/2 inactivation. J Cell Biochem. 2018; 119(9):7377-7387. DOI: 10.1002/jcb.27041. View

Tanabe A, Tanikawa K, Tsunetomi M, Takai K, Ikeda H, Konno J . RNA helicase YTHDC2 promotes cancer metastasis via the enhancement of the efficiency by which HIF-1α mRNA is translated. Cancer Lett. 2016; 376(1):34-42. DOI: 10.1016/j.canlet.2016.02.022. View

Xu Y, Ye S, Zhang N, Zheng S, Liu H, Zhou K . The FTO/miR-181b-3p/ARL5B signaling pathway regulates cell migration and invasion in breast cancer. Cancer Commun (Lond). 2020; 40(10):484-500. PMC: 7571404. DOI: 10.1002/cac2.12075. View

Tan X, Fu J, Yuan Z, Zhu L, Fu L . ACNPD: The Database for Elucidating the Relationships Between Natural Products, Compounds, Molecular Mechanisms, and Cancer Types. Front Pharmacol. 2021; 12:746067. PMC: 8419280. DOI: 10.3389/fphar.2021.746067. View

Zhang Y, Liu S, Zhao T, Dang C . METTL3‑mediated m6A modification of Bcl‑2 mRNA promotes non‑small cell lung cancer progression. Oncol Rep. 2021; 46(2). PMC: 8218297. DOI: 10.3892/or.2021.8114. View

Abby E, Tourpin S, Ribeiro J, Daniel K, Messiaen S, Moison D . Implementation of meiosis prophase I programme requires a conserved retinoid-independent stabilizer of meiotic transcripts. Nat Commun. 2016; 7:10324. PMC: 4729902. DOI: 10.1038/ncomms10324. View

Henamayee S, Banik K, Sailo B, Shabnam B, Harsha C, Srilakshmi S . Therapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties. Molecules. 2020; 25(10). PMC: 7288145. DOI: 10.3390/molecules25102278. View

10.

Suthar A, Banavalikar M, Biyani M . Pharmacological activities of Genistein, an isoflavone from soy (Glycine max): part I--anti-cancer activity. Indian J Exp Biol. 2003; 39(6):511-9. View

11.

Fu B, Wang N, Tan H, Li S, Cheung F, Feng Y . Multi-Component Herbal Products in the Prevention and Treatment of Chemotherapy-Associated Toxicity and Side Effects: A Review on Experimental and Clinical Evidences. Front Pharmacol. 2018; 9:1394. PMC: 6281965. DOI: 10.3389/fphar.2018.01394. View

12.

Wang Y, Li Y, Yue M, Wang J, Kumar S, Wechsler-Reya R . N-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications. Nat Neurosci. 2018; 21(2):195-206. PMC: 6317335. DOI: 10.1038/s41593-017-0057-1. View

13.

Rauf A, Imran M, Ali Khan I, Ur-Rehman M, Gilani S, Mehmood Z . Anticancer potential of quercetin: A comprehensive review. Phytother Res. 2018; 32(11):2109-2130. DOI: 10.1002/ptr.6155. View

14.

Meyer K . DART-seq: an antibody-free method for global mA detection. Nat Methods. 2019; 16(12):1275-1280. PMC: 6884681. DOI: 10.1038/s41592-019-0570-0. View

15.

Wang C, Zhang C, Chen L, Anderson S, Lu F, Yuan C . Colon cancer chemopreventive effects of baicalein, an active enteric microbiome metabolite from baicalin. Int J Oncol. 2015; 47(5):1749-58. PMC: 4599184. DOI: 10.3892/ijo.2015.3173. View

16.

Newman D, Cragg G . Natural Products as Sources of New Drugs from 1981 to 2014. J Nat Prod. 2016; 79(3):629-61. DOI: 10.1021/acs.jnatprod.5b01055. View

17.

Shah A, Rashid F, Awan H, Hu S, Wang X, Chen L . The DEAD-Box RNA Helicase DDX3 Interacts with mA RNA Demethylase ALKBH5. Stem Cells Int. 2018; 2017:8596135. PMC: 5733242. DOI: 10.1155/2017/8596135. View

18.

Rong B, Zhang Q, Wan J, Xing S, Dai R, Li Y . Ribosome 18S mA Methyltransferase METTL5 Promotes Translation Initiation and Breast Cancer Cell Growth. Cell Rep. 2020; 33(12):108544. DOI: 10.1016/j.celrep.2020.108544. View

19.

Huang H, Weng H, Chen J . mA Modification in Coding and Non-coding RNAs: Roles and Therapeutic Implications in Cancer. Cancer Cell. 2020; 37(3):270-288. PMC: 7141420. DOI: 10.1016/j.ccell.2020.02.004. View

20.

Wang H, Zhang K, Liu J, Yang J, Tian Y, Yang C . Curcumin Regulates Cancer Progression: Focus on ncRNAs and Molecular Signaling Pathways. Front Oncol. 2021; 11:660712. PMC: 8072122. DOI: 10.3389/fonc.2021.660712. View