{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:05:32Z","timestamp":1777586732252,"version":"3.51.4"},"reference-count":144,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Epigenetic alterations, particularly RNA methylation, play a crucial role in many types of disease development and progression. Among them, N6-methyladenosine (m6A) is the most common epigenetic RNA modification, and its important roles are not only related to the occurrence, progression, and aggressiveness of tumors but also affect the progression of many non-tumor diseases. The biological effects of RNA m6A modification are dynamically and reversibly regulated by methyltransferases (writers), demethylases (erasers), and m6A binding proteins (readers). This review summarized the current finding of the RNA m6A modification regulators in male infertility and genital system tumors and discussed the role and potential clinical application of the RNA m6A modification in spermatogenesis and male genital system tumors.<\/jats:p>","DOI":"10.3389\/fcell.2021.676364","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T06:04:57Z","timestamp":1621404297000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Role of RNA N6-Methyladenosine Modification in Male Infertility and Genital System Tumors"],"prefix":"10.3389","volume":"9","author":[{"given":"Shuai","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongfeng","family":"Lao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuefeng","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunchang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolong","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhilong","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1016\/j.cell.2015.08.011","article-title":"HNRNPA2B1 Is a Mediator of mA-Dependent Nuclear RNA Processing Events.","volume":"162","author":"Alarc\u00f3n","year":"2015","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"4000","DOI":"10.1200\/jco.2016.68.7798","article-title":"Genetic Determinants of Cisplatin Resistance in Patients With Advanced Germ Cell Tumors.","volume":"34","author":"Bagrodia","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26116","article-title":"The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline.","volume":"6","author":"Bailey","year":"2017","journal-title":"eLife"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11091316","article-title":"Molecular Basis of Cisplatin Resistance in Testicular Germ Cell Tumors.","volume":"11","author":"Bakardjieva-Mihaylova","year":"2019","journal-title":"Cancers"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12040771","article-title":"VIRMA-Dependent N6-Methyladenosine Modifications Regulate the Expression of Long Non-Coding RNAs CCAT1 and CCAT2 in Prostate Cancer.","volume":"12","author":"Barros-Silva","year":"2020","journal-title":"Cancers"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2657","DOI":"10.1007\/s00018-012-1186-z","article-title":"Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs): post-transcriptional drivers of cancer progression?","volume":"70","author":"Bell","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"B7","first-page":"1233","article-title":"Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase.","volume":"3","author":"Bokar","year":"1997","journal-title":"RNA"},{"key":"B8","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"B9","doi-asserted-by":"publisher","first-page":"9143","DOI":"10.2147\/ott.S226796","article-title":"RNA mA Methyltransferase METTL3 Promotes The Growth Of Prostate Cancer By Regulating Hedgehog Pathway.","volume":"12","author":"Cai","year":"2019","journal-title":"Onco Targets Ther."},{"key":"B10","doi-asserted-by":"publisher","first-page":"4845","DOI":"10.1182\/blood-2011-06-362830","article-title":"Increased incidence of non-Hodgkin lymphoma, leukemia, and myeloma in patients with diabetes mellitus type 2: a meta-analysis of observational studies.","volume":"119","author":"Castillo","year":"2012","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.3249","article-title":"YTHDC1 gene polymorphisms and hepatoblastoma susceptibility in Chinese children: A seven-center case-control study.","volume":"22","author":"Chen","year":"2020","journal-title":"J. Gene Med."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02847-6","article-title":"WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an mA-dependent manner.","volume":"11","author":"Chen","year":"2020","journal-title":"Cell Death Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1080\/15548627.2020.1720431","article-title":"mA mRNA methylation regulates testosterone synthesis through modulating autophagy in Leydig cells.","volume":"17","author":"Chen","year":"2020","journal-title":"Autophagy"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1158\/1055-9965.Epi-10-0031","article-title":"International trends in the incidence of testicular cancer, 1973-2002.","volume":"19","author":"Chia","year":"2010","journal-title":"Cancer Epidemiol. Biomarkers. Prev."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00571","article-title":"Emerging Prognostic Biomarkers in Testicular Germ Cell Tumors: Looking Beyond Established Practice.","volume":"8","author":"Chovanec","year":"2018","journal-title":"Front. Oncol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2622","DOI":"10.1016\/j.celrep.2017.02.059","article-title":"mA RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells.","volume":"18","author":"Cui","year":"2017","journal-title":"Cell Rep."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05539-0","article-title":"A widespread alternate form of cap-dependent mRNA translation initiation.","volume":"9","author":"de la Parra","year":"2018","journal-title":"Nat. Commun."},{"key":"B18","doi-asserted-by":"publisher","first-page":"3971","DOI":"10.1073\/pnas.71.10.3971","article-title":"Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells.","volume":"71","author":"Desrosiers","year":"1974","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B19","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1038\/ng2048","article-title":"Variation in FTO contributes to childhood obesity and severe adult obesity.","volume":"39","author":"Dina","year":"2007","journal-title":"Nat. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/nature11112","article-title":"Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq.","volume":"485","author":"Dominissini","year":"2012","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.rbmo.2015.05.004","article-title":"The question of sperm DNA fragmentation testing in the male infertility work-up: a response to Professor Lewis\u2019 commentary.","volume":"31","author":"Drobnis","year":"2015","journal-title":"Reprod. Biomed. Online"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-020-01735-3","article-title":"Activation of the KDM5A\/miRNA-495\/YTHDF2\/m6A-MOB3B axis facilitates prostate cancer progression.","volume":"39","author":"Du","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12626","article-title":"YTHDF2 destabilizes mA-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex.","volume":"7","author":"Du","year":"2016","journal-title":"Nat. Commun."},{"key":"B24","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/s0015-028238400-x","article-title":"Etiologic factors in 1294 consecutive cases of male infertility.","volume":"22","author":"Dubin","year":"1971","journal-title":"Fertil. Steril."},{"key":"B25","first-page":"3182","article-title":"General Motors Cancer Research Prizewinners Laureates Lectures. Charles F. Kettering Prize. Clinical trials in testicular cancer.","volume":"71","author":"Einhorn","year":"1993","journal-title":"Cancer"},{"key":"B26","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1517\/14728222.2014.920324","article-title":"Germline copy number variation in the YTHDC2 gene: does it have a role in finding a novel potential molecular target involved in pancreatic adenocarcinoma susceptibility?","volume":"18","author":"Fanale","year":"2014","journal-title":"Expert Opin. Ther. Targets"},{"key":"B27","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1126\/science.1141634","article-title":"A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity.","volume":"316","author":"Frayling","year":"2007","journal-title":"Science"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2812","DOI":"10.1158\/0008-5472.Can-18-3592","article-title":"N-Methylation of Adenosine of FZD10 mRNA Contributes to PARP Inhibitor Resistance.","volume":"79","author":"Fukumoto","year":"2019","journal-title":"Cancer Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2320","DOI":"10.1002\/cncr.30597","article-title":"Future of testicular germ cell tumor incidence in the United States: Forecast through 2026.","volume":"123","author":"Ghazarian","year":"2017","journal-title":"Cancer"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1056\/NEJMoa003005","article-title":"Sperm morphology, motility, and concentration in fertile and infertile men.","volume":"345","author":"Guzick","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-019-0916-x","article-title":"Anti-tumour immunity controlled through mRNA mA methylation and YTHDF1 in dendritic cells.","volume":"566","author":"Han","year":"2019","journal-title":"Nature"},{"key":"B32","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.ccell.2019.12.007","article-title":"Epigenetic Silencing of CDR1as Drives IGF2BP3-Mediated Melanoma Invasion and Metastasis.","volume":"37","author":"Hanniford","year":"2020","journal-title":"Cancer Cell"},{"key":"B33","doi-asserted-by":"publisher","first-page":"3909","DOI":"10.1091\/mbc.10.11.3909","article-title":"The interaction and colocalization of Sam68 with the splicing-associated factor YT521-B in nuclear dots is regulated by the Src family kinase p59(fyn).","volume":"10","author":"Hartmann","year":"1999","journal-title":"Mol. Biol. Cell"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.01166","article-title":"mA Reader YTHDC2 Promotes Radiotherapy Resistance of Nasopharyngeal Carcinoma via Activating IGF1R\/AKT\/S6 Signaling Axis.","volume":"10","author":"He","year":"2020","journal-title":"Front. Oncol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1038\/cr.2017.99","article-title":"Ythdc2 is an N-methyladenosine binding protein that regulates mammalian spermatogenesis.","volume":"27","author":"Hsu","year":"2017","journal-title":"Cell Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/s41556-018-0045-z","article-title":"Recognition of RNA N-methyladenosine by IGF2BP proteins enhances mRNA stability and translation.","volume":"20","author":"Huang","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2235-4","article-title":"YTHDF2 promotes spermagonial adhesion through modulating MMPs decay via mA\/mRNA pathway.","volume":"11","author":"Huang","year":"2020","journal-title":"Cell Death Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.ccell.2019.03.006","article-title":"Small-Molecule Targeting of Oncogenic FTO Demethylase in Acute Myeloid Leukemia.","volume":"35","author":"Huang","year":"2019","journal-title":"Cancer Cell"},{"key":"B39","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1093\/nar\/gku1276","article-title":"Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5.","volume":"43","author":"Huang","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1093\/humupd\/8.2.183","article-title":"Selected genetic factors associated with male infertility.","volume":"8","author":"Huynh","year":"2002","journal-title":"Hum. Reprod. Update"},{"key":"B41","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1101\/gad.333369.119","article-title":"The rRNA mA methyltransferase METTL5 is involved in pluripotency and developmental programs.","volume":"34","author":"Ignatova","year":"2020","journal-title":"Genes Dev."},{"key":"B42","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/ng.2571","article-title":"A variant in FTO shows association with melanoma risk not due to BMI.","volume":"45","author":"Iles","year":"2013","journal-title":"Nat. Genet"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.30919","article-title":"ketu mutant mice uncover an essential meiotic function for the ancient RNA helicase YTHDC2.","volume":"7","author":"Jain","year":"2018","journal-title":"eLife"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-10-49","article-title":"Common variants in mismatch repair genes associated with increased risk of sperm DNA damage and male infertility.","volume":"10","author":"Ji","year":"2012","journal-title":"BMC Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1038\/nchembio.687","article-title":"N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO.","volume":"7","author":"Jia","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-019-0830-6","article-title":"mA mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis.","volume":"12","author":"Jin","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007412","article-title":"Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development.","volume":"14","author":"Kasowitz","year":"2018","journal-title":"PLoS Genet."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1093\/humrep\/16.11.2347","article-title":"Pregnancy achieved following ICSI from a man with Klinefelter\u2019s syndrome and spinal cord injury.","volume":"16","author":"Kyono","year":"2001","journal-title":"Hum. Reprod."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1016\/j.fertnstert.2016.01.002","article-title":"Sequencing of FTO and ALKBH5 in men undergoing infertility work-up identifies an infertility-associated variant and two missense mutations.","volume":"105","author":"Landfors","year":"2016","journal-title":"Fertil. Steril"},{"key":"B50","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/nature18954","article-title":"eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation.","volume":"536","author":"Lee","year":"2016","journal-title":"Nature"},{"key":"B51","first-page":"1012","article-title":"METTL3 enhances cell adhesion through stabilizing integrin \u03b21 mRNA via an m6A-HuR-dependent mechanism in prostatic carcinoma.","volume":"10","author":"Li","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1038\/cr.2014.153","article-title":"Structure of the YTH domain of human YTHDF2 in complex with an mA mononucleotide reveals an aromatic cage for mA recognition.","volume":"24","author":"Li","year":"2014","journal-title":"Cell Res."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01267-6","article-title":"YTHDF2 mediates the mRNA degradation of the tumor suppressors to induce AKT phosphorylation in N6-methyladenosine-dependent way in prostate cancer.","volume":"19","author":"Li","year":"2020","journal-title":"Mol. Cancer"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1436-y","article-title":"Ythdf2-mediated mA mRNA clearance modulates neural development in mice.","volume":"19","author":"Li","year":"2018","journal-title":"Genome Biol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"20159","DOI":"10.1073\/pnas.1918986117","article-title":"ALKBH5 regulates anti-PD-1 therapy response by modulating lactate and suppressive immune cell accumulation in tumor microenvironment.","volume":"117","author":"Li","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-1038-7","article-title":"METTL3 facilitates tumor progression via an mA-IGF2BP2-dependent mechanism in colorectal carcinoma.","volume":"18","author":"Li","year":"2019","journal-title":"Mol. Cancer"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.10385","article-title":"The m6A reader protein YTHDC2 is a potential biomarker and associated with immune infiltration in head and neck squamous cell carcinoma.","volume":"8","author":"Li","year":"2020","journal-title":"PeerJ"},{"key":"B58","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1038\/s41422-018-0072-0","article-title":"Suppression of mA reader Ythdf2 promotes hematopoietic stem cell expansion.","volume":"28","author":"Li","year":"2018","journal-title":"Cell Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.ccell.2016.11.017","article-title":"FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N-Methyladenosine RNA Demethylase.","volume":"31","author":"Li","year":"2017","journal-title":"Cancer Cell"},{"key":"B60","doi-asserted-by":"publisher","first-page":"4983","DOI":"10.1038\/s41388-020-1349-6","article-title":"Deoxycholic acid modulates the progression of gallbladder cancer through N-methyladenosine-dependent microRNA maturation.","volume":"39","author":"Lin","year":"2020","journal-title":"Oncogene"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1038\/cr.2017.117","article-title":"Mettl3-\/Mettl14-mediated mRNA N-methyladenosine modulates murine spermatogenesis.","volume":"27","author":"Lin","year":"2017","journal-title":"Cell Res."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108120","article-title":"YTHDF2\/3 Are Required for Somatic Reprogramming through Different RNA Deadenylation Pathways.","volume":"32","author":"Liu","year":"2020","journal-title":"Cell Rep."},{"key":"B63","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/nchembio.1432","article-title":"A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation.","volume":"10","author":"Liu","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03148-8","article-title":"The mechanism of mA methyltransferase METTL3-mediated autophagy in reversing gefitinib resistance in NSCLC cells by \u03b2-elemene.","volume":"11","author":"Liu","year":"2020","journal-title":"Cell Death Dis."},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-019-1837-z","article-title":"mA RNA modification and its writer\/reader VIRMA\/YTHDF3 in testicular germ cell tumors: a role in seminoma phenotype maintenance.","volume":"17","author":"Lobo","year":"","journal-title":"J. Transl. Med."},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11101535","article-title":"Detailed Characterization of Immune Cell Infiltrate and Expression of Immune Checkpoint Molecules PD-L1\/CTLA-4 and MMR Proteins in Testicular Germ Cell Tumors Disclose Novel Disease Biomarkers.","volume":"11","author":"Lobo","year":"","journal-title":"Cancers"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11091233","article-title":"The Oncogene Metadherin Interacts with the Known Splicing Proteins YTHDC1, Sam68 and T-STAR and Plays a Novel Role in Alternative mRNA Splicing.","volume":"11","author":"Luxton","year":"2019","journal-title":"Cancers"},{"key":"B68","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41589-018-0184-3","article-title":"N(6-)Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation.","volume":"15","author":"Ma","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101801","article-title":"The mA reader YTHDC2 inhibits lung adenocarcinoma tumorigenesis by suppressing SLC7A11-dependent antioxidant function.","volume":"38","author":"Ma","year":"2021","journal-title":"Redox Biol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"3565","DOI":"10.26355\/eurrev_202004_20817","article-title":"m6A methyltransferase METTL3 promotes the progression of prostate cancer via m6A-modified LEF1.","volume":"24","author":"Ma","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13317-9","article-title":"mA in mRNA coding regions promotes translation via the RNA helicase-containing YTHDC2.","volume":"10","author":"Mao","year":"2019","journal-title":"Nat. Commun."},{"key":"B72","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1016\/j.molcel.2018.08.004","article-title":"Methylation of Structured RNA by the mA Writer METTL16 Is Essential for Mouse Embryonic Development.","volume":"71","author":"Mendel","year":"2018","journal-title":"Mol. Cell"},{"key":"B73","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/j.cell.2015.10.012","article-title":"5\u2019 UTR mA Promotes Cap-Independent Translation.","volume":"163","author":"Meyer","year":"2015","journal-title":"Cell"},{"key":"B74","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1016\/j.cell.2012.05.003","article-title":"Comprehensive analysis of mRNA methylation reveals enrichment in 3\u2019 UTRs and near stop codons.","volume":"149","author":"Meyer","year":"2012","journal-title":"Cell"},{"key":"B75","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1038\/s41591-019-0376-8","article-title":"Targeting epigenetic modifications in cancer therapy: erasing the roadmap to cancer.","volume":"25","author":"Mohammad","year":"2019","journal-title":"Nat. Med."},{"key":"B76","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1002\/1097-0142(19910301)67:5<1305::AID-CNCR2820670506>3.0.CO;2-J","article-title":"Salvage chemotherapy for patients with germ cell tumors. The Memorial Sloan-Kettering Cancer Center experience (1979-1989).","volume":"67","author":"Motzer","year":"1991","journal-title":"Cancer"},{"key":"B77","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1111\/andr.12612","article-title":"N6-Methyladenosine detected in RNA of testicular germ cell tumors is controlled by METTL3, ALKBH5, YTHDC1\/F1\/F2, and HNRNPC as writers, erasers, and readers.","volume":"7","author":"Nettersheim","year":"2019","journal-title":"Andrology"},{"key":"B78","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1038\/sj.bjc.6605058","article-title":"Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer.","volume":"100","author":"Nilsson","year":"2009","journal-title":"Br. J. Cancer"},{"key":"B79","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1016\/s0140-673609899-9","article-title":"Spermatozoal RNA profiles of normal fertile men.","volume":"360","author":"Ostermeier","year":"2002","journal-title":"Lancet"},{"key":"B80","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.cell.2017.05.003","article-title":"The U6 snRNA mA Methyltransferase METTL16 Regulates SAM Synthetase Intron Retention.","volume":"169","author":"Pendleton","year":"2017","journal-title":"Cell"},{"key":"B81","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/0092-867490159-2","article-title":"The methylated constituents of L cell messenger RNA: evidence for an unusual cluster at the 5\u2019 terminus.","volume":"4","author":"Perry","year":"1975","journal-title":"Cell"},{"key":"B82","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/cr.2014.3","article-title":"Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase.","volume":"24","author":"Ping","year":"2014","journal-title":"Cell Res."},{"key":"B83","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1093\/nar\/gkz1147","article-title":"The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA.","volume":"48","author":"Pinto","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"18956","DOI":"10.1002\/jcb.29216","article-title":"MicroRNAs associated with lung squamous cell carcinoma: New prognostic biomarkers and therapeutic targets.","volume":"120","author":"Qi","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"B85","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nrg.2015.10","article-title":"Unique features of long non-coding RNA biogenesis and function.","volume":"17","author":"Quinn","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"B86","doi-asserted-by":"publisher","first-page":"3359","DOI":"10.1080\/21691401.2019.1649273","article-title":"The circular RNA circ-ITCH acts as a tumour suppressor in osteosarcoma via regulating miR-22.","volume":"47","author":"Ren","year":"2019","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12923-x","article-title":"Structure and regulation of ZCCHC4 in mA-methylation of 28S rRNA.","volume":"10","author":"Ren","year":"2019","journal-title":"Nat. Commun."},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.31311","article-title":"YTHDC1 mediates nuclear export of N-methyladenosine methylated mRNAs.","volume":"6","author":"Roundtree","year":"2017","journal-title":"eLife"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0030115","article-title":"Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.","volume":"3","author":"Scuteri","year":"2007","journal-title":"PLoS Genet."},{"key":"B90","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/cr.2017.15","article-title":"YTHDF3 facilitates translation and decay of N-methyladenosine-modified RNA.","volume":"27","author":"Shi","year":"2017","journal-title":"Cell Res."},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12801-6","article-title":"YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression.","volume":"10","author":"Shi","year":"2019","journal-title":"Nat. Commun."},{"key":"B92","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer Statistics, 2021.","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.18434","article-title":"Structural insights into the molecular mechanism of the mA writer complex.","volume":"5","author":"\u015aled\u017a","year":"2016","journal-title":"eLife"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1016\/j.ejca.2008.11.004","article-title":"Overweight, obesity and risk of haematological malignancies: a cohort study of Swedish and Finnish twins.","volume":"45","author":"S\u00f6derberg","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"B95","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/s0968-000402189-8","article-title":"YTH: a new domain in nuclear proteins.","volume":"27","author":"Stoilov","year":"2002","journal-title":"Trends Biochem. Sci."},{"key":"B96","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.cell.2017.11.031","article-title":"R-2HG Exhibits Anti-tumor Activity by Targeting FTO\/mA\/MYC\/CEBPA Signaling.","volume":"172","author":"Su","year":"2018","journal-title":"Cell"},{"key":"B97","doi-asserted-by":"publisher","first-page":"3269","DOI":"10.1111\/1759-7714.13667","article-title":"Downregulation of m A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non-small cell lung cancer.","volume":"11","author":"Sun","year":"2020","journal-title":"Thorac. Cancer"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03049-w","article-title":"N-methyladenosine-dependent pri-miR-17-92 maturation suppresses PTEN\/TMEM127 and promotes sensitivity to everolimus in gastric cancer.","volume":"11","author":"Sun","year":"2020","journal-title":"Cell Death Dis."},{"key":"B99","doi-asserted-by":"publisher","first-page":"621","DOI":"10.3892\/ijo.2017.4219","article-title":"The epitranscriptome m6A writer METTL3 promotes chemo- and radioresistance in pancreatic cancer cells.","volume":"52","author":"Taketo","year":"2018","journal-title":"Int. J. Oncol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.canlet.2016.02.022","article-title":"RNA helicase YTHDC2 promotes cancer metastasis via the enhancement of the efficiency by which HIF-1\u03b1 mRNA is translated.","volume":"376","author":"Tanabe","year":"2016","journal-title":"Cancer Lett."},{"key":"B101","doi-asserted-by":"publisher","first-page":"E325","DOI":"10.1073\/pnas.1717794115","article-title":"ALKBH5-dependent m6A demethylation controls splicing and stability of long 3\u2019-UTR mRNAs in male germ cells.","volume":"115","author":"Tang","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B102","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41422-020-0279-8","article-title":"mA-dependent biogenesis of circular RNAs in male germ cells.","volume":"30","author":"Tang","year":"2020","journal-title":"Cell Res."},{"key":"B103","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.semcancer.2019.05.021","article-title":"MicroRNA heterogeneity in melanoma progression.","volume":"59","author":"Thyagarajan","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"B104","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/s2213-858730043-2","article-title":"Concepts in diagnosis and therapy for male reproductive impairment.","volume":"5","author":"Tournaye","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28730-1","article-title":"Comparison of Image-Guided Intensity-Modulated Radiotherapy and Low-dose Rate Brachytherapy with or without External Beam Radiotherapy in Patients with Localized Prostate Cancer.","volume":"8","author":"Tsubokura","year":"2018","journal-title":"Sci. Rep."},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1038\/srep42271","article-title":"AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells.","volume":"7","author":"Ueda","year":"2017","journal-title":"Sci. Rep."},{"key":"B107","doi-asserted-by":"publisher","first-page":"7719","DOI":"10.1093\/nar\/gkz619","article-title":"The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112.","volume":"47","author":"van Tran","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B108","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1590\/s1677-55382008000100008","article-title":"Sperm defect severity rather than sperm Source is associated with lower fertilization rates after intracytoplasmic sperm injection.","volume":"34","author":"Verza","year":"2008","journal-title":"Int. Braz. J. Urol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1038\/onc.2017.351","article-title":"Essential role of METTL3-mediated mA modification in glioma stem-like cells maintenance and radioresistance.","volume":"37","author":"Visvanathan","year":"2018","journal-title":"Oncogene"},{"key":"B110","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.urology.2006.02.045","article-title":"Incidence of testicular germ cell cancers in U.S. children: SEER program experience 1973 to 2000. Urology","author":"Walsh","year":"2006"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020104514","article-title":"m A RNA methyltransferases METTL3\/14 regulate immune responses to anti-PD-1 therapy.","volume":"39","author":"Wang","year":"2020","journal-title":"EMBO J."},{"key":"B112","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.molcel.2016.05.041","article-title":"Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases.","volume":"63","author":"Wang","year":"2016","journal-title":"Mol. Cell."},{"key":"B113","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/nature18298","article-title":"Structural basis of N-adenosine methylation by the METTL3-METTL14 complex.","volume":"534","author":"Wang","year":"2016","journal-title":"Nature"},{"key":"B114","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/nature12730","article-title":"N6-methyladenosine-dependent regulation of messenger RNA stability.","volume":"505","author":"Wang","year":"2014","journal-title":"Nature"},{"key":"B115","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1016\/j.cell.2015.05.014","article-title":"N-methyladenosine Modulates Messenger RNA Translation Efficiency.","volume":"161","author":"Wang","year":"2015","journal-title":"Cell"},{"key":"B116","doi-asserted-by":"publisher","first-page":"2004","DOI":"10.15252\/embr.201744940","article-title":"Human METTL16 is a N-methyladenosine (mA) methyltransferase that targets pre-mRNAs and various non-coding RNAs.","volume":"18","author":"Warda","year":"2017","journal-title":"EMBO Rep."},{"key":"B117","doi-asserted-by":"publisher","first-page":"11366","DOI":"10.1111\/jcmm.15738","article-title":"METTL3 potentiates resistance to cisplatin through m A modification of TFAP2C in seminoma.","volume":"24","author":"Wei","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"B118","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1016\/j.molcel.2018.02.015","article-title":"Zc3h13 Regulates Nuclear RNA mA Methylation and Mouse Embryonic Stem Cell Self-Renewal.","volume":"69","author":"Wen","year":"2018","journal-title":"Mol. Cell."},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01293-4","article-title":"Long non-coding RNA NEAT1 promotes bone metastasis of prostate cancer through N6-methyladenosine.","volume":"19","author":"Wen","year":"2020","journal-title":"Mol. Cancer"},{"key":"B120","doi-asserted-by":"publisher","first-page":"742","DOI":"10.4103\/1008-682x.155536","article-title":"Posttesticular sperm maturation, infertility, and hypercholesterolemia.","volume":"17","author":"Whitfield","year":"2015","journal-title":"Asian J. Androl."},{"key":"B121","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.molcel.2017.09.021","article-title":"Regulation of mA Transcripts by the 3\u2032\u21925\u2032 RNA Helicase YTHDC2 Is Essential for a Successful Meiotic Program in the Mammalian Germline.","volume":"68","author":"Wojtas","year":"2017","journal-title":"Mol. Cell"},{"key":"B122","doi-asserted-by":"publisher","first-page":"682","DOI":"10.7150\/jca.46379","article-title":"N6-methyladenosine RNA methylation regulators contribute to the progression of prostate cancer.","volume":"12","author":"Wu","year":"2021","journal-title":"J. Cancer"},{"key":"B123","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1534\/genetics.117.300574","article-title":"Mettl3 Mutation Disrupts Gamete Maturation and Reduces Fertility in Zebrafish.","volume":"208","author":"Xia","year":"2018","journal-title":"Genetics"},{"key":"B124","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.molcel.2016.01.012","article-title":"Nuclear mA Reader YTHDC1 Regulates mRNA Splicing.","volume":"61","author":"Xiao","year":"2016","journal-title":"Mol. Cell"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01281-8","article-title":"N-methyladenosine-modified CircRNA-SORE sustains sorafenib resistance in hepatocellular carcinoma by regulating \u03b2-catenin signaling.","volume":"19","author":"Xu","year":"2020","journal-title":"Mol. Cancer"},{"key":"B126","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1038\/cr.2017.100","article-title":"Mettl3-mediated mA regulates spermatogonial differentiation and meiosis initiation.","volume":"27","author":"Xu","year":"2017","journal-title":"Cell Res."},{"key":"B127","doi-asserted-by":"publisher","first-page":"3906","DOI":"10.1093\/nar\/gky130","article-title":"N6-Methyladenosine modification of lincRNA 1281 is critically required for mESC differentiation potential.","volume":"46","author":"Yang","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10669-0","article-title":"mA mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade.","volume":"10","author":"Yang","year":"2019","journal-title":"Nat. Commun."},{"key":"B129","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/cr.2017.31","article-title":"Extensive translation of circular RNAs driven by N-methyladenosine.","volume":"27","author":"Yang","year":"2017","journal-title":"Cell Res."},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1038\/srep24345","article-title":"Increased N6-methyladenosine in Human Sperm RNA as a Risk Factor for Asthenozoospermia.","volume":"6","author":"Yang","year":"2016","journal-title":"Sci. Rep."},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061323","article-title":"m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response.","volume":"20","author":"Yu","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B132","doi-asserted-by":"publisher","first-page":"3588","DOI":"10.7150\/jca.42338","article-title":"The M6A methyltransferase METTL3 promotes the development and progression of prostate carcinoma via mediating MYC methylation.","volume":"11","author":"Yuan","year":"2020","journal-title":"J. Cancer"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-018-0019-0","article-title":"VIRMA mediates preferential mA mRNA methylation in 3\u2019UTR and near stop codon and associates with alternative polyadenylation.","volume":"4","author":"Yue","year":"2018","journal-title":"Cell Discov"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2020.144810","article-title":"Critical roles of mRNA mA modification and YTHDC2 expression for meiotic initiation and progression in female germ cells.","volume":"753","author":"Zeng","year":"2020","journal-title":"Gene"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-3079","article-title":"ALKBH5 promotes the proliferation of renal cell carcinoma by regulating AURKB expression in an mA-dependent manner.","volume":"8","author":"Zhang","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-1116-x","article-title":"mA modification-mediated CBX8 induction regulates stemness and chemosensitivity of colon cancer via upregulation of LGR5.","volume":"18","author":"Zhang","year":"2019","journal-title":"Mol. Cancer"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03186-2","article-title":"YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA.","volume":"11","author":"Zhang","year":"2020","journal-title":"Cell Death Dis."},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2020.115627","article-title":"Increased m6A modification of RNA methylation related to the inhibition of demethylase FTO contributes to MEHP-induced Leydig cell injury(star).","volume":"268","author":"Zhao","year":"2021","journal-title":"Environ. Pollut."},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2020.113911","article-title":"Increased m6A RNA modification is related to the inhibition of the Nrf2-mediated antioxidant response in di-(2-ethylhexyl) phthalate-induced prepubertal testicular injury.","volume":"259","author":"Zhao","year":"2020","journal-title":"Environ. Pollut."},{"key":"B140","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.molcel.2012.10.015","article-title":"ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.","volume":"49","author":"Zheng","year":"2013","journal-title":"Mol. Cell"},{"key":"B141","doi-asserted-by":"publisher","first-page":"2262","DOI":"10.1016\/j.celrep.2017.08.027","article-title":"Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs.","volume":"20","author":"Zhou","year":"2017","journal-title":"Cell Rep."},{"key":"B142","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1002\/mc.22782","article-title":"FTO regulates the chemo-radiotherapy resistance of cervical squamous cell carcinoma (CSCC) by targeting \u03b2-catenin through mRNA demethylation.","volume":"57","author":"Zhou","year":"2018","journal-title":"Mol. Carcinog."},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119180","article-title":"The FTO mA demethylase inhibits the invasion and migration of prostate cancer cells by regulating total mA levels.","volume":"271","author":"Zhu","year":"2021","journal-title":"Life Sci."},{"key":"B144","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1038\/cr.2014.152","article-title":"Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine.","volume":"24","author":"Zhu","year":"2014","journal-title":"Cell Res."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.676364\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T10:11:03Z","timestamp":1622110263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.676364\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,19]]},"references-count":144,"alternative-id":["10.3389\/fcell.2021.676364"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.676364","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,19]]},"article-number":"676364"}}