Therapeutic effect and transcriptome-methylome characteristics of METTL3 inhibition in liver hepatocellular carcinoma

Balacco DL, Soller M. The m(6)A writer: rise of a machine for growing tasks. Biochemistry. 2019;58(5):363–78.

Article  CAS  PubMed  Google Scholar 

Lence T, Paolantoni C, Worpenberg L, Roignant JY. Mechanistic insights into m(6)A RNA enzymes. Biochim Biophys Acta Gene Regul Mech. 2019;1862(3):222–9.

Article  CAS  PubMed  Google Scholar 

Liu J, Yue Y, Han D, Wang X, Fu Y, Zhang L, Jia G, Yu M, Lu Z, Deng X, et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol. 2014;10(2):93–5.

Article  CAS  PubMed  Google Scholar 

Ping XL, Sun BF, Wang L, Xiao W, Yang X, Wang WJ, Adhikari S, Shi Y, Lv Y, Chen YS, et al. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 2014;24(2):177–89.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Deng X, Su R, Weng H, Huang H, Li Z, Chen J. RNA N(6)-methyladenosine modification in cancers: current status and perspectives. Cell Res. 2018;28(5):507–17.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang YG, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol. 2011;7(12):885–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tang C, Klukovich R, Peng H, Wang Z, Yu T, Zhang Y, Zheng H, Klungland A, Yan W. ALKBH5-dependent m6A demethylation controls splicing and stability of long 3′-UTR mRNAs in male germ cells. Proc Natl Acad Sci USA. 2018;115(2):E325–33.

Article  CAS  PubMed  Google Scholar 

Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang CM, Li CJ, Vagbo CB, Shi Y, Wang WL, Song SH, et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell. 2013;49(1):18–29.

Article  CAS  PubMed  Google Scholar 

Wang X, Lu Z, Gomez A, Hon GC, Yue Y, Han D, Fu Y, Parisien M, Dai Q, Jia G, et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature. 2014;505(7481):117–20.

Article  PubMed  Google Scholar 

Wang X, Zhao BS, Roundtree IA, Lu Z, Han D, Ma H, Weng X, Chen K, Shi H, He C. N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell. 2015;161(6):1388–99.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhao Q, Zhao Y, Hu W, Zhang Y, Wu X, Lu J, Li M, Li W, Wu W, Wang J, et al. m(6)A RNA modification modulates PI3K/Akt/mTOR signal pathway in gastrointestinal cancer. Theranostics. 2020;10(21):9528–43.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shi H, Wang X, Lu Z, Zhao BS, Ma H, Hsu PJ, Liu C, He C. YTHDF3 facilitates translation and decay of N(6)-methyladenosine-modified RNA. Cell Res. 2017;27(3):315–28.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xiao W, Adhikari S, Dahal U, Chen YS, Hao YJ, Sun BF, Sun HY, Li A, Ping XL, Lai WY, et al. Nuclear m(6)A Reader YTHDC1 regulates mRNA splicing. Mol Cell. 2016;61(4):507–19.

Article  CAS  PubMed  Google Scholar 

Roundtree IA, Luo GZ, Zhang Z, Wang X, Zhou T, Cui Y, Sha J, Huang X, Guerrero L, Xie P, et al. YTHDC1 mediates nuclear export of N(6)-methyladenosine methylated mRNAs. Elife. 2017;6:e31311.

Article  PubMed  PubMed Central  Google Scholar 

Zhao BS, Roundtree IA, He C. Post-transcriptional gene regulation by mRNA modifications. Nat Rev Mol Cell Biol. 2017;18(1):31–42.

Article  CAS  PubMed  Google Scholar 

Wang X, Feng J, Xue Y, Guan Z, Zhang D, Liu Z, Gong Z, Wang Q, Huang J, Tang C, et al. Structural basis of N(6)-adenosine methylation by the METTL3-METTL14 complex. Nature. 2016;534(7608):575–8.

Article  CAS  PubMed  Google Scholar 

Lee H, Bao S, Qian Y, Geula S, Leslie J, Zhang C, Hanna JH, Ding L. Stage-specific requirement for Mettl3-dependent m(6)A mRNA methylation during haematopoietic stem cell differentiation. Nat Cell Biol. 2019;21(6):700–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu K, Yang Y, Feng GH, Sun BF, Chen JQ, Li YF, Chen YS, Zhang XX, Wang CX, Jiang LY, et al. Mettl3-mediated m(6)A regulates spermatogonial differentiation and meiosis initiation. Cell Res. 2017;27(9):1100–14.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiang X, Liu B, Nie Z, Duan L, Xiong Q, Jin Z, Yang C, Chen Y. The role of m6A modification in the biological functions and diseases. Signal Transduct Target Ther. 2021;6(1):74.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li T, Hu PS, Zuo Z, Lin JF, Li X, Wu QN, Chen ZH, Zeng ZL, Wang F, Zheng J, et al. METTL3 facilitates tumor progression via an m(6)A-IGF2BP2-dependent mechanism in colorectal carcinoma. Mol Cancer. 2019;18(1):112.

Article  PubMed  PubMed Central  Google Scholar 

Chen M, Wei L, Law CT, Tsang FH, Shen J, Cheng CL, Tsang LH, Ho DW, Chiu DK, Lee JM, et al. RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2. Hepatology. 2018;67(6):2254–70.

Article  CAS  PubMed  Google Scholar 

Su R, Dong L, Li C, Nachtergaele S, Wunderlich M, Qing Y, Deng X, Wang Y, Weng X, Hu C, et al. R-2HG exhibits anti-tumor activity by targeting FTO/m(6)A/MYC/CEBPA signaling. Cell. 2018;172(1–2):90-105e123.

Article  CAS  PubMed  Google Scholar 

Huang H, Weng H, Sun W, Qin X, Shi H, Wu H, Zhao BS, Mesquita A, Liu C, Yuan CL, et al. Recognition of RNA N(6)-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol. 2018;20(3):285–95.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang S, Yang C, Yang Z, Zhang D, Ma X, Mills G, Liu Z. Homeostasis of redox status derived from glucose metabolic pathway could be the key to understanding the Warburg effect. Am J Cancer Res. 2015;5(4):1265–80.

PubMed  PubMed Central  Google Scholar 

Wang W, Shao F, Yang X, Wang J, Zhu R, Yang Y, Zhao G, Guo D, Sun Y, Wang J, et al. METTL3 promotes tumour development by decreasing APC expression mediated by APC mRNA N(6)-methyladenosine-dependent YTHDF binding. Nat Commun. 2021;12(1):3803.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lin S, Choe J, Du P, Triboulet R, Gregory RI. The m(6)A methyltransferase METTL3 promotes translation in human cancer cells. Mol Cell. 2016;62(3):335–45.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang C, Samanta D, Lu H, Bullen JW, Zhang H, Chen I, He X, Semenza GL. Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m(6)A-demethylation of NANOG mRNA. Proc Natl Acad Sci USA. 2016;113(14):E2047-2056.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu L, Wang J, Sun G, Wu Q, Ma J, Zhang X, Huang N, Bian Z, Gu S, Xu M, et al. m(6)A mRNA methylation regulates CTNNB1 to promote the proliferation of hepatoblastoma. Mol Cancer. 2019;18(1):188.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, Li B, Liu XS. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res. 2017;77(21):e108–10.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D. The human genome browser at UCSC. Genome Res. 2002;12(6):996–1006.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47(W1):W556–60.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM, Bindal N, Boutselakis H, Cole CG, Creatore C, Dawson E, et al. COSMIC: the catalogue of somatic mutations in cancer. Nucleic Acids Res. 2019;47(D1):D941–7.

Article  CAS  PubMed  Google Scholar 

Koch A, De Meyer T, Jeschke J, Van Criekinge W. MEXPRESS: visualizing expression, DNA methylation and clinical TCGA data. BMC Genomics. 2015;16(1):636.

Article  PubMed  PubMed Central 

Comments (0)

No login
gif