{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:16:47Z","timestamp":1793114207988,"version":"4.5.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81502350"],"award-info":[{"award-number":["81502350"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472521"],"award-info":[{"award-number":["81472521"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81402251"],"award-info":[{"award-number":["81402251"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672676"],"award-info":[{"award-number":["81672676"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772890"],"award-info":[{"award-number":["81772890"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81502350"],"award-info":[{"award-number":["81502350"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81502350"],"award-info":[{"award-number":["81502350"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007162","name":"Guangdong Science and Technology Department","doi-asserted-by":"publisher","award":["2016A030313352"],"award-info":[{"award-number":["2016A030313352"]}],"id":[{"id":"10.13039\/501100007162","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Abnormal expression of long-noncoding RNA is involved in the tumorigenesis and progression of various cancers, but the potential molecular regulatory mechanisms are unclear. Microbial flora and chronic inflammation, such as periodontitis, which is associated with oral cancer, affect the occurrence and progression of tumors. Accordingly, we stimulated the tongue squamous cell carcinoma (TSCC) cell lines CAL27 and SCC15 with a low concentration of lipopolysaccharide (LPS) from <jats:italic>Porphyromonas gingivalis<\/jats:italic> (P.g) for 6 days and then performed LncRNA sequencing on P.g-LPS-treated CAL27 cells and untreated CAL27 cells. LTSCCAT was upregulated in P.g-LPS-treated CAL27 cells compared with untreated CAL27 cells. LTSCCAT induced epithelial\u2013mesenchymal transition and promoted the invasion and metastasis of TSCC in vitro and in vivo. LncRNA LTSCCAT was upregulated in TSCC patients with periodontitis and was correlated with metastasis and poor prognosis. We predicted through an online database and confirmed by dual-luciferase reporter assays that LTSCCAT is a competitive endogenous RNA for the regulation of miR-103a-2-5p. Another dual-luciferase reporter assay confirmed that miR-103a-2-5p has a binding site at the 3\u2032-UTR of the histone methylation transferase SMYD3 and inhibits its translation. Chromatin immunoprecipitation experiments demonstrated that SMYD3 binds directly to the promoter region of TWIST1 and promotes its transcription, which is related to H3K4 trimethylation. The effect of pcDNA\/LTSCCAT on expression was attenuated by miR-103a-2-5p mimics. The RF and SVM classifier predicts that LTSCCAT can bind to SMYD3, whereas the RNA immunoprecipitation (RIP) assay confirms that it cannot. In addition, we predicted the combination of LTSCCAT and SMYD3 through software, but the RIP assay confirmed that LTSCCAT could not be combined with SMYD3. For the first time, we showed that periodontitis promotes the invasion and metastasis of TSCC and clarified the molecular mechanism of LTSCCAT to promote invasion and metastasis of TSCC, providing a potential therapeutic target for clinical treatment of TSCC.<\/jats:p>","DOI":"10.1038\/s41419-021-03415-2","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T10:05:38Z","timestamp":1612433138000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["LncRNA LTSCCAT promotes tongue squamous cell carcinoma metastasis via targeting the miR-103a-2-5p\/SMYD3\/TWIST1 axis"],"prefix":"10.1038","volume":"12","author":[{"given":"Mo","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingwen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanming","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiqing","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixiong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junming","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqi","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LuoDan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"3415_CR1","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.oraloncology.2010.06.006","volume":"46","author":"IO Bello","year":"2010","unstructured":"Bello, I. O., Soini, Y. & Salo, T. Prognostic evaluation of oral tongue cancer: means, markers and perspectives (I). Oral. Oncol. 46, 630\u2013635 (2010).","journal-title":"Oral. Oncol."},{"key":"3415_CR2","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.oraloncology.2010.06.008","volume":"46","author":"IO Bello","year":"2010","unstructured":"Bello, I. O., Soini, Y. & Salo, T. Prognostic evaluation of oral tongue cancer: means, markers and perspectives (II). Oral. Oncol. 46, 636\u2013643 (2010).","journal-title":"Oral. Oncol."},{"key":"3415_CR3","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1053\/j.gastro.2018.10.054","volume":"156","author":"W Zhuo","year":"2019","unstructured":"Zhuo, W. et al. Long noncoding RNA GMAN, up-regulated in gastric cancer tissues, is associated with metastasis in patients and promotes translation of ephrin A1 by competitively binding GMAN-AS. Gastroenterology 156, 676\u2013691.e11 (2019).","journal-title":"Gastroenterology"},{"key":"3415_CR4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06152-x","volume":"9","author":"C Chen","year":"2018","unstructured":"Chen, C. et al. LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment. Nat. Commun. 9, 3826 (2018).","journal-title":"Nat. Commun."},{"key":"3415_CR5","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1016\/j.ymthe.2018.04.002","volume":"26","author":"Z Lin","year":"2018","unstructured":"Lin, Z. et al. Chemotherapy-Induced Long Non-coding RNA 1 Promotes Metastasis and Chemo-Resistance of TSCC via the Wnt\/beta-Catenin Signaling Pathway. Mol. Ther.: J. Am. Soc. Gene Ther. 26, 1494\u20131508 (2018).","journal-title":"Mol. Ther.: J. Am. Soc. Gene Ther."},{"key":"3415_CR6","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/j.cell.2006.02.016","volume":"124","author":"M Karin","year":"2006","unstructured":"Karin, M., Lawrence, T. & Nizet, V. Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. Cell 124, 823\u2013835 (2006).","journal-title":"Cell"},{"key":"3415_CR7","doi-asserted-by":"publisher","first-page":"2528","DOI":"10.1002\/ijc.31011","volume":"141","author":"V Eklof","year":"2017","unstructured":"Eklof, V. et al. Cancer-associated fecal microbial markers in colorectal cancer detection. Int. J. cancer 141, 2528\u20132536 (2017).","journal-title":"Int. J. cancer"},{"key":"3415_CR8","first-page":"326","volume":"67","author":"AP Bhatt","year":"2017","unstructured":"Bhatt, A. P., Redinbo, M. R. & Bultman, S. J. The role of the microbiome in cancer development and therapy. CA: a cancer J. clinicians 67, 326\u2013344 (2017).","journal-title":"CA: a cancer J. clinicians"},{"key":"3415_CR9","first-page":"679","volume":"175","author":"V Singh","year":"2018","unstructured":"Singh, V. et al. Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver. Cancer Cell 175, 679\u2013694.e22 (2018).","journal-title":"Cancer Cell"},{"key":"3415_CR10","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1016\/j.biopha.2016.09.082","volume":"84","author":"P Gholizadeh","year":"2016","unstructured":"Gholizadeh, P. et al. Role of oral microbiome on oral cancers, a review. Biomedicine Pharmacother. = Biomedecine pharmacotherapie 84, 552\u2013558 (2016).","journal-title":"Biomedicine Pharmacother. = Biomedecine pharmacotherapie"},{"key":"3415_CR11","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/jre.12407","volume":"52","author":"YL Cheng","year":"2017","unstructured":"Cheng, Y. L. et al. Chronic periodontitis can affect the levels of potential oral cancer salivary mRNA biomarkers. J. periodontal Res. 52, 428\u2013437 (2017).","journal-title":"J. periodontal Res."},{"key":"3415_CR12","doi-asserted-by":"publisher","first-page":"22613","DOI":"10.18632\/oncotarget.4209","volume":"6","author":"A Binder Gallimidi","year":"2015","unstructured":"Binder Gallimidi, A. et al. Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model. Oncotarget 6, 22613\u201322623 (2015).","journal-title":"Oncotarget"},{"key":"3415_CR13","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1001\/archotol.133.5.450","volume":"133","author":"M Tezal","year":"2007","unstructured":"Tezal, M. et al. Chronic periodontitis and the risk of tongue cancer. Arch. Otolaryngol. -head. neck Surg. 133, 450\u2013454 (2007).","journal-title":"Arch. Otolaryngol. -head. neck Surg."},{"key":"3415_CR14","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.cyto.2016.07.013","volume":"86","author":"NH Ha","year":"2016","unstructured":"Ha, N. H. et al. Porphyromonas gingivalis increases the invasiveness of oral cancer cells by upregulating IL-8 and MMPs. Cytokine 86, 64\u201372 (2016).","journal-title":"Cytokine"},{"key":"3415_CR15","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.ccell.2016.01.013","volume":"29","author":"ME Sarris","year":"2016","unstructured":"Sarris, M. E., Moulos, P., Haroniti, A., Giakountis, A. & Talianidis, I. Smyd3 Is a Transcriptional Potentiator of Multiple Cancer-Promoting Genes and Required for Liver and Colon Cancer Development. Cancer cell 29, 354\u2013366 (2016).","journal-title":"Cancer cell"},{"key":"3415_CR16","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/nature13320","volume":"510","author":"PK Mazur","year":"2014","unstructured":"Mazur, P. K. et al. SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer. Nature 510, 283\u2013287 (2014).","journal-title":"Nature"},{"key":"3415_CR17","doi-asserted-by":"publisher","first-page":"4438","DOI":"10.1093\/nar\/gkr019","volume":"39","author":"S Xu","year":"2011","unstructured":"Xu, S., Wu, J., Sun, B., Zhong, C. & Ding, J. Structural and biochemical studies of human lysine methyltransferase Smyd3 reveal the important functional roles of its post-SET and TPR domains and the regulation of its activity by DNA binding. Nucleic acids Res 39, 4438\u20134449 (2011).","journal-title":"Nucleic acids Res"},{"key":"3415_CR18","doi-asserted-by":"publisher","first-page":"340","DOI":"10.4161\/epi.19506","volume":"7","author":"GS Van Aller","year":"2012","unstructured":"Van Aller, G. S. et al. Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation. Epigenetics 7, 340\u2013343 (2012).","journal-title":"Epigenetics"},{"key":"3415_CR19","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/ncb1151","volume":"6","author":"R Hamamoto","year":"2004","unstructured":"Hamamoto, R. et al. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat. cell Biol. 6, 731\u2013740 (2004).","journal-title":"Nat. cell Biol."},{"key":"3415_CR20","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1093\/nar\/gkx1259","volume":"46","author":"XD Zhang","year":"2018","unstructured":"Zhang, X. D. et al. The interaction of lncRNA EZR-AS1 with SMYD3 maintains overexpression of EZR in ESCC cells. Nucleic acids Res 46, 1793\u20131809 (2018).","journal-title":"Nucleic acids Res"},{"key":"3415_CR21","doi-asserted-by":"publisher","first-page":"3271","DOI":"10.1016\/j.febslet.2012.06.049","volume":"586","author":"B Zeng","year":"2012","unstructured":"Zeng, B. et al. Epigenetic regulation of miR-124 by hepatitis C virus core protein promotes migration and invasion of intrahepatic cholangiocarcinoma cells by targeting SMYD3. FEBS Lett. 586, 3271\u20133278 (2012).","journal-title":"FEBS Lett."},{"key":"3415_CR22","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1158\/0008-5472.CAN-11-1052","volume":"72","author":"AM Cock-Rada","year":"2012","unstructured":"Cock-Rada, A. M. et al. SMYD3 promotes cancer invasion by epigenetic upregulation of the metalloproteinase MMP-9. Cancer Res 72, 810\u2013820 (2012).","journal-title":"Cancer Res"},{"key":"3415_CR23","doi-asserted-by":"publisher","first-page":"6043","DOI":"10.1158\/0008-5472.CAN-16-0500","volume":"76","author":"CH Tsai","year":"2016","unstructured":"Tsai, C. H. et al. SMYD3-Mediated H2A.Z.1 Methylation Promotes Cell Cycle and Cancer Proliferation. Cancer Res 76, 6043\u20136053 (2016).","journal-title":"Cancer Res"},{"key":"3415_CR24","doi-asserted-by":"crossref","unstructured":"Fenizia C., et al. SMYD3 promotes the epithelial-mesenchymal transition in breast cancer. Nucleic acids research. 2018.","DOI":"10.1093\/nar\/gky1221"},{"key":"3415_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00304-1","volume":"8","author":"YX Song","year":"2017","unstructured":"Song, Y. X. et al. Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion. Nat. Commun. 8, 289 (2017).","journal-title":"Nat. Commun."},{"key":"3415_CR26","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/nrg.2016.20","volume":"17","author":"DW Thomson","year":"2016","unstructured":"Thomson, D. W. & Dinger, M. E. Endogenous microRNA sponges: evidence and controversy. Nat. Rev. Genet. 17, 272\u2013283 (2016).","journal-title":"Nat. Rev. Genet."},{"key":"3415_CR27","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/nature12986","volume":"505","author":"Y Tay","year":"2014","unstructured":"Tay, Y., Rinn, J. & Pandolfi, P. P. The multilayered complexity of ceRNA crosstalk and competition. Nature 505, 344\u2013352 (2014).","journal-title":"Nature"},{"issue":"Suppl 2","key":"3415_CR28","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-S2-S4","volume":"14","author":"TH Chang","year":"2013","unstructured":"Chang, T. H. et al. An enhanced computational platform for investigating the roles of regulatory RNA and for identifying functional RNA motifs. BMC Bioinforma. 14(Suppl 2), S4 (2013).","journal-title":"BMC Bioinforma."},{"key":"3415_CR29","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1093\/epirev\/mxx006","volume":"39","author":"DS Michaud","year":"2017","unstructured":"Michaud, D. S., Fu, Z., Shi, J. & Chung, M. Periodontal Disease, Tooth Loss, and Cancer Risk. Epidemiol. Rev. 39, 49\u201358 (2017).","journal-title":"Epidemiol. Rev."},{"key":"3415_CR30","first-page":"173","volume":"67","author":"MK Barton","year":"2017","unstructured":"Barton, M. K. Evidence accumulates indicating periodontal disease as a risk factor for colorectal cancer or lymphoma. CA: a cancer J. clinicians 67, 173\u2013174 (2017).","journal-title":"CA: a cancer J. clinicians"},{"key":"3415_CR31","first-page":"5021","volume":"21","author":"PF Manicone","year":"2017","unstructured":"Manicone, P. F. et al. Dental health in patients affected by alcohol use disorders: a cross-sectional study. Eur. Rev. Med. Pharmacol. Sci. 21, 5021\u20135027 (2017).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"3415_CR32","doi-asserted-by":"publisher","first-page":"493","DOI":"10.3389\/fcimb.2017.00493","volume":"7","author":"J Lee","year":"2017","unstructured":"Lee, J. et al. Human Primary Epithelial Cells Acquire an Epithelial-Mesenchymal-Transition Phenotype during Long-Term Infection by the Oral Opportunistic Pathogen. Porphyromonas gingivalis. Front. Cell. Infect. Microbiol. 7, 493 (2017).","journal-title":"Porphyromonas gingivalis. Front. Cell. Infect. Microbiol."},{"key":"3415_CR33","doi-asserted-by":"publisher","first-page":"209","DOI":"10.4248\/IJOS11075","volume":"3","author":"J Katz","year":"2011","unstructured":"Katz, J., Onate, M. D., Pauley, K. M., Bhattacharyya, I. & Cha, S. Presence of Porphyromonas gingivalis in gingival squamous cell carcinoma. Int. J. oral. Sci. 3, 209\u2013215 (2011).","journal-title":"Int. J. oral. Sci."},{"key":"3415_CR34","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3389\/fcimb.2017.00057","volume":"7","author":"F Geng","year":"2017","unstructured":"Geng, F. et al. Persistent Exposure to Porphyromonas gingivalis Promotes Proliferative and Invasion Capabilities, and Tumorigenic Properties of Human Immortalized Oral Epithelial Cells. Front. Cell. Infect. Microbiol. 7, 57 (2017).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"3415_CR35","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1111\/cmi.12554","volume":"18","author":"MN Sztukowska","year":"2016","unstructured":"Sztukowska, M. N. et al. Porphyromonas gingivalis initiates a mesenchymal-like transition through ZEB1 in gingival epithelial cells. Cell. Microbiol. 18, 844\u2013858 (2016).","journal-title":"Cell. Microbiol."},{"key":"3415_CR36","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/j.cell.2014.10.013","volume":"159","author":"Z Xing","year":"2014","unstructured":"Xing, Z. et al. lncRNA directs cooperative epigenetic regulation downstream of chemokine signals. Cell 159, 1110\u20131125 (2014).","journal-title":"Cell"},{"key":"3415_CR37","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1038\/nsmb.2480","volume":"20","author":"TR Mercer","year":"2013","unstructured":"Mercer, T. R. & Mattick, J. S. Structure and function of long noncoding RNAs in epigenetic regulation. Nat. Struct. Mol. Biol. 20, 300\u2013307 (2013).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"3415_CR38","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/nrc.2017.118","volume":"18","author":"T Brabletz","year":"2018","unstructured":"Brabletz, T., Kalluri, R., Nieto, M. A. & Weinberg, R. A. EMT in cancer. Nat. Rev. Cancer 18, 128\u2013134 (2018).","journal-title":"Nat. Rev. Cancer"},{"key":"3415_CR39","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1038\/nrm3758","volume":"15","author":"S Lamouille","year":"2014","unstructured":"Lamouille, S., Xu, J. & Derynck, R. Molecular mechanisms of epithelial-mesenchymal transition. Nat. Rev. Mol. cell Biol. 15, 178\u2013196 (2014).","journal-title":"Nat. Rev. Mol. cell Biol."},{"key":"3415_CR40","first-page":"1","volume":"9","author":"L Huang","year":"2017","unstructured":"Huang, L. & Xu, A. M. S. E. T. and MYND domain containing protein 3 in cancer. Am. J. Transl. Res. 9, 1\u201314 (2017).","journal-title":"Am. J. Transl. Res."},{"key":"3415_CR41","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1038\/nrm1761","volume":"6","author":"C Martin","year":"2005","unstructured":"Martin, C. & Zhang, Y. The diverse functions of histone lysine methylation. Nat. Rev. Mol. cell Biol. 6, 838\u2013849 (2005).","journal-title":"Nat. Rev. Mol. cell Biol."},{"key":"3415_CR42","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nature01080","volume":"419","author":"H Santos-Rosa","year":"2002","unstructured":"Santos-Rosa, H. et al. Active genes are tri-methylated at K4 of histone H3. Nature 419, 407\u2013411 (2002).","journal-title":"Nature"},{"key":"3415_CR43","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/ncb1076","volume":"6","author":"R Schneider","year":"2004","unstructured":"Schneider, R. et al. Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat. cell Biol. 6, 73\u201377 (2004).","journal-title":"Nat. cell Biol."},{"key":"3415_CR44","doi-asserted-by":"publisher","first-page":"5994","DOI":"10.1111\/j.1742-4658.2008.06728.x","volume":"275","author":"M Rentoft","year":"2008","unstructured":"Rentoft, M., Kim, K., Cho, Y., Lee, C. H. & Kim, A. Enhancer requirement for histone methylation linked with gene activation. FEBS J. 275, 5994\u20136001 (2008).","journal-title":"FEBS J."}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-03415-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-03415-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-03415-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T18:25:04Z","timestamp":1669919104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-021-03415-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,1]]},"references-count":44,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["3415"],"URL":"https:\/\/doi.org\/10.1038\/s41419-021-03415-2","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,1]]},"assertion":[{"value":"8 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethics Committee approval was obtained from the Institutional Ethics Committee of Sun Yat-sen Cancer Center.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"144"}}