m6A RNA甲基化修饰影响恶性肿瘤及肿瘤干细胞生物学特性的研究进展

doi:10.11904/j.issn.1002-3070.2022.06.011

Abstract

Abstract: N6-methyladenosine(m6A)methylation is a dynamic reversible reaction under the co-regulation of methyltransferase,demethyltransferase,the m6A-specific protein-YT521-B homology(YTH)structure family,insulin-like growth factor 2(IGF2BPs)and heterogeneous nuclear ribonucleoproteins(HNRNPs).It is currently the most studied as RNA pre-transcriptional modifications.Basic and clinical studies have found that under the interaction between various modifying enzymes and tumor genes,m6A methylation modification not only affects the occurrence of tumors,but also regulates the proliferation and differentiation of cancer stem cells,thereby promoting the development and distant metastasis of malignant tumors.Therefore,further study of m6A methylation modification will help to clarify the pathogenesis of malignant tumors and further improve the treatment strategy of malignant tumors.

Key words: N6-methyladenosine, Tumor cells, Cancer stem cells

CLC Number:

R730

WANG Xinyi, LU Yiping, SUN Zhengrong. Research progress on the effects of m6A RNA methylation modification on the biological characteristics of malignant tumors and tumor stem cells[J]. Journal of Practical Oncology, 2022, 36(6): 551-555.

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URL: http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/10.11904/j.issn.1002-3070.2022.06.011

http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/Y2022/V36/I6/551

References

1 Li YY.Modern epigenetics methods in biological research[J].Methods,2021,187:104-113.
2 Ban Y,Tan PQ,Cai J,et al.LNCAROD is stabilized by m6A methylation and promotes cancer progression via forming a ternary complex with HSPA1A and YBX1 in head and neck squamous cell carcinoma[J].Mol Oncol,2020,14(6):1282-1296.
3 李慧,庞达.m6A甲基化修饰在肿瘤中的作用[J].实用肿瘤学杂志,2020,34(5):480-484.
4 Roundtree IA,Molly EE,Tao P,et al.Dynamic RNA modifications in gene expression regulation[J].Cell,2017,169(7):1187-1200.
5 Zhao W,Qi XQ,Liu L,et al.Epigenetic regulation of m6A modifications in human cancer[J].Mol Ther Nucleic Acids,2020,19:405-412.
6 Zeng CW,Huang WX,Li YQ,et al.Roles of METTL3 in cancer:mechanisms and therapeutic targeting[J].J Hematol Oncol,2020,13(1):117.
7 Meyer KD,Jaffrey SR.Rethinking m6A readers,writers,and erasers[J].Annu Rev Cell Dev Biol,2017,33:319-342.
8 Wang X,Zhao BS,Roundtreeet IA,et al.N6-methyladenosine modulates messenger RNA translation efficiency[J].Cell,2015,161(6):1388-1399.
9 Allis CD,Jenuwein T.The molecular hallmarks of epigenetic control[J].Nat Rev Genet,2016,17(8):487-500.
10 Chang GQ,Leu JS,Ma L,et al.Methylation of RNA N6-methyladenosine in modulation of cytokine responses and tumorigenesis[J].Cytokine,2019,118:35-41.
11 Wang X,Feng J,Xue Y,et al.Structural basis of N6-adenosine methylation by the METTL3-METTL14 complex[J].Nature,2016,534(7608):575-578.
12 Cai JR,Yang F,Zhan HL,et al.RNA m6A methyltransferase METTL3 promotes the growth of prostate cancer by regulating hedgehog pathway[J].Onco Targets Ther,2019,12:9143-9152.
13 Yang ZJ,Ma JW,Han SX,et al.ZFAS1 exerts an oncogenic role via suppressing miR-647 in an m6A-dependent manner in cervical cancer[J].Onco Targets Ther,2020,13:11795-11806.
14 Lang FC,Singh RK,Pei YG,et al.EBV epitranscriptome reprogramming by METTL14 is critical for viral-associated tumorigenesis[J].PLoS Pathog,2019,15(6):e1007796.
15 Attard G,Parker C,Eeles RA,et al.Prostate cancer[J].Lancet,2016,387(10013):70-82.
16 Wang P,Wang XT,Zheng L,et al.Gene signatures and prognostic values of m6A regulators in hepatocellular carcinoma[J].Front Genet,2020,11:540186.
17 Wang XK,Zhang YW,Wang CM,et al.METTL16 promotes cell proliferation by up-regulating cyclin D1 expression in gastric cancer[J].J Cell Mol Med,2021,25(14):6602-6617.
18 Liu JZ,Yue YA,Han DL,et al.A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation[J].Nat Chem Biol,2014,10(2):93-95.
19 Little NA,Hastie ND,Davies RC.Identification of WTAP,a novel Wilms′ tumour 1-associating protein[J].Hum Mol Genet,2000,9(5):2231-2239.
20 Chen YH,Peng CH,Chen JR,et al.WTAP facilitates progression of hepatocellular carcinoma via m6A-HuR-dependent epigenetic silencing of ETS1[J].Mol Cancer,2019,18(1):127.
21 刘培培,杨梦雪,严雪冰.m6A甲基化修饰在消化系统肿瘤中的研究进展[J].国际肿瘤学杂志,2021,48(1):688-692.
22 Chen SJ,Li YZ,Zhi S,et al.WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m6A-dependent manner[J].Cell Death Dis,2020,11(8):659.
23 Zheng GQ,Dahl JA,Niuet Y,et al.ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility[J].Mol Cell,2013,49(1):18-29.
24 Zhao X,Yang Y,Sun BF,et al.FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis[J].Cell Res,2014,24(2):1403-1419.
25 Wang TY,Kong S,Tao M,et al.The potential role of RNA N6-methyladenosine in cancer progression[J].Mol Cancer,2020,19(1):88.
26 Zou DL,Dong L,Li CY,et al.The m6A eraser FTO facilitates proliferation and migration of human cervical cancer cells[J].Cancer Cell Int,2019,19:321.
27 Niu Y,Lin ZY,Wan A,et al.RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3[J].Mol Cancer,2019,18(1):46.
28 Zhang L,Wan YC,Zhang ZH,et al.FTO demethylates m6A modifications in HOXB13 mRNA and promotes endometrial cancer metastasis by activating the WNT signalling pathway[J].RNA Biol,2021,18(9):1-14.
29 Zhou S,Bai ZL,Xia D,et al.FTO regulates the chemo-radiotherapy resistance of cervical squamous cell carcinoma(CSCC)by targeting β-catenin through mRNA demethylation[J].Mol Carcinog,2018,57(5):590-597.
30 Deng XL,Su R,Weng HY,et al.RNA N6-methyladenosine modification in cancers:current status and perspectives[J].Cell Res,2018,28(5):507-517.
31 Shen C,Sheng Y,Zhu AC,et al.RNA demethylase ALKBH5 selectively promotes tumorigenesis and cancer stem cell self-renewal in acute myeloid leukemia[J].Cell Stem Cell,2020,27(1):64-80.
32 Patil DP,Pickering BF,JaffreyReading SR.m6A in the transcriptome:m6A-binding proteins[J].Trends Cell Biol,2018,28(2):113-127.
33 Li FX,Yi Y,Miao YY,et al.N6-methyladenosine modulates nonsense-mediated mRNA decay in human glioblastoma[J].Cancer Res,2019,79(22):5785-5798.
34 Kretschmer J,Rao H,Hackert P,et al.The m6A reader protein YTHDC2 interacts with the small ribosomal subunit and the 5′-3′ exoribonuclease XRN1[J].Rna,2018,24(10):1339-1350.
35 Dominissini D,Moshkovitz SM,Schwartz S,et al.Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq[J].Nature,2012,485(7397):201-206.
36 Hou JJ,Zhang H,Liu J,et al.YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma[J].Mol Cancer,2019,18(1):163.
37 Yang Z,Li J,Feng GX,et al.MicroRNA-145 modulates N6-methyladenosine levels by targeting the 3′-untranslated mRNA region of the N6-methyladenosine binding YTH domain family 2 protein[J].J Biol Chem,2017,292(9):3614-3623.
38 Liu SP,Li GH,Li QJ,et al.The roles and mechanisms of YTH domain-containing proteins in cancer development and progression[J].Am J Cancer Res,2020,10(4):1068-1084.
39 Bell JL,Wchter K,Mühleck B,et al.Insulin-like growth factor 2 mRNA-binding proteins(IGF2BPs):post-transcriptional drivers of cancer progression[J].Cell Mol Life Sci,2013,70(15):2657-2675.
40 Huang HL,Weng HY,WJ,et al.Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation[J].Nat Cell Biol,2018,20(3):285-295.
41 Huang GZ,Wu QQ,Zheng ZN,et al.m6A-Related bioinformatics analysis reveals that HNRNPC facilitates progression of OSCC via EMT[J].Aging(Albany NY),2020,12(12):11667-11684.
42 Xu LC,Pan JX,Pan HD.Construction and validation of an m6A RNA methylation regulators-based prognostic signature for esophageal cancer[J].Cancer Manag Res,2020,12:5385-5394.
43 Guo HM,Wang B,Xu KY,et al.m(6)A reader HNRNPA2B1 promotes esophageal cancer progression via up-regulation of ACLY and ACC1[J].Front Oncol,2020,10:553045.
44 Liu T,Wei QL,Jin J,et al.The m6A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation[J].Nucleic Acids Res,2020,48(7):3816-3831.
45 Han JY,Won M,Kim JH,et al.Cancer stem cell-targeted bio-imaging and chemotherapeutic perspective[J].Chem Soc Rev,2020,49(22):7856-7878.
46 Ma ZH,Ji JF.N6-methyladenosine(m6A)RNA modification in cancer stem cells[J].Stem Cells,2020,38(12):1511-1519.
47 Visvanathan A,Patil V,Arora A,et al.Essential role of METTL3-mediated m6A modification in glioma stem-like cells maintenance and radioresistance[J].Oncogene,2018,37(4):522-533.
48 Xu Y,Liu J,Chen WJ,et al.Regulation of N6-methyladenosine in the differentiation of cancer stem cells and their fate[J].Front Cell Dev Biol,2020,8:561703.
49 Zhang Y,Kang M,Zhang B,et al.m6A modification-mediated CBX8 induction regulates stemness and chemosensitivity of colon cancer via upregulation of LGR5[J].Mol Cancer,2019,18(1):185.
50 Relier S,Ripoll J,Guillorit H,et al.FTO-mediated cytoplasmic m6Am demethylation adjusts stem-like properties in colorectal cancer cell[J].Nat Commun,2021,12(1):1716.
51 Su R,Dong L,Li YC,et al.Targeting FTO suppresses cancer stem cell maintenance and immune evasion[J].Cancer Cell,2020,38(1):79-96.
52 Zhang CZ,Samanta D,Lu HQ,et al.Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA[J].Proc Natl Acad Sci U S A,2016,113(14):2047-2056.
53 Kowalski-Chauvel A,Lacore MG,Arnauduc F,et al.The m6A RNA demethylase ALKBH5 promotes radioresistance and invasion capability of glioma stem cells[J].Cancers(Basel),2020,13(1):40.
54 Zhang CZ,Huang SZ,Zhuang HK,et al.YTHDF2 promotes the liver cancer stem cell phenotype and cancer metastasis by regulating OCT4 expression via m6A RNA methylation[J].Oncogene,2020,39(23):4507-4518.
55 Yang YC,Wu J,Liu FQ,et al.IGF2BP1 promotes the liver cancer stem cell phenotype by regulating MGAT5 mRNA stability by m6A RNA methylation[J].Stem Cells Dev,2021,30(22):1115-1125.

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[3]	WANG Yu, QIAO Juanjuan, ZHANG Lei, LIU Siwei, YANG Shucai. The role of steroid hormones in breast cancer and its effect on cancer stem cells [J]. Journal of Practical Oncology, 2019, 33(5): 466-470.
[4]	XU Xunzheng, ZHANG Haogang, QIAO Pengfei, WANG Fujing. Clinical efficacy and practicability analysis of circulating tumor cells [J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(2): 169-173.
[5]	OUYANG Zhongrui, CHAI Shuang, ZHAO Haiqi, LIU Yaohua. Research progress of PERK signaling pathway under endoplasmic reticulum stress in tumor [J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(1): 38-41.
[6]	HUANG Qianqian, MA Jianjia, WU Qiang, LIU Binbin, MU Xiaoqin, LIU Shulin. Research progress on tumor stem cells and tumor targeted therapy [J]. PRACTICAL ONCOLOGY JOURNAL, 2017, 31(6): 533-537.
[7]	LUO Bin ,SHI Qihui ,LIU Jiaxiang ,TIAN Jianhui. The clinical significance of circulating tumor cells in lung cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2016, 30(4): 370-374.
[8]	CAI Li, SONG Xiaowei, PAN Lihua, SHI Guangyue, LIU Wei, SUN Lichun, CHEN Xuesong, ZHAO Lina. The significance of epithelial mesenchymal transitions gene Twist in circulating tumor cells to efficacy of chemotherapy in metastatic breast cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2013, 27(1): 37-41.
[9]	TANG Dabei,ZHANG Qingyuan,WANG Jingxuan,ZHAO Shu,ZHAO Wenhui. A clinical study of estradiol therapy in endocrine-resistant advanced breast cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2012, 26(4): 289-292.
[10]	QIAN Liuqi,LIU Qian,LIU Yi,ZHANG Shaohua,WANG Tao,WU Shikai,SONG Santai,LIU Bing,JIANG Zefei. Expression of circulating tumor cells in metastatic breast cancer patients and its relationship with multiple serum tumor markers [J]. PRACTICAL ONCOLOGY JOURNAL, 2012, 26(3): 220-224.

Research progress on the effects of m6A RNA methylation modification on the biological characteristics of malignant tumors and tumor stem cells

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