Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.
Google ScholarÂ
You JS, Jones PA. Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell. 2012;22:9–20.
Google ScholarÂ
Jung G, Hernandez-Illan E, Moreira L, Balaguer F, Goel A. Epigenetics of colorectal cancer: biomarker and therapeutic potential. Nat Rev Gastroenterol Hepatol. 2020;17:111–30.
Google ScholarÂ
Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet. 2012;13:343–57.
Google ScholarÂ
Zhang X, Huang Y, Shi X. Emerging roles of lysine methylation on non-histone proteins. Cell Mol Life Sci. 2015;72:4257–72.
Google ScholarÂ
Bao Y, Ma Y, Huang W, Bai Y, Gao S, Xiu L, et al. Regulation of autophagy and cellular signaling through non-histone protein methylation. Int J Biol Macromol. 2025;291:139057.
Google ScholarÂ
Hamamoto R, Saloura V, Nakamura Y. Critical roles of non-histone protein lysine methylation in human tumorigenesis. Nat Rev Cancer. 2015;15:110–24.
Google ScholarÂ
Di Blasi R, Blyuss O, Timms JF, Conole D, Ceroni F, Whitwell HJ. Non-histone protein methylation: Biological significance and bioengineering potential. ACS Chem Biol. 2021;16:238–50.
Google ScholarÂ
Chen Q, Hu Q, Chen Y, Shen N, Zhang N, Li A, et al. PRMT6 methylation of STAT3 regulates tumor metastasis in breast cancer. Cell Death Dis. 2023;14:655.
Google ScholarÂ
Huang L, Zhang XO, Rozen EJ, Sun X, Sallis B, Verdejo-Torres O, et al. PRMT5 activates AKT via methylation to promote tumor metastasis. Nat Commun. 2022;13:3955.
Google ScholarÂ
Beck DB, Oda H, Shen SS, Reinberg D. PR-Set7 and H4K20me1: at the crossroads of genome integrity, cell cycle, chromosome condensation, and transcription. Genes Dev. 2012;26:325–37.
Google ScholarÂ
Jorgensen S, Schotta G, Sorensen CS. Histone H4 lysine 20 methylation: key player in epigenetic regulation of genomic integrity. Nucleic Acids Res. 2013;41:2797–806.
Google ScholarÂ
Shi X, Kachirskaia I, Yamaguchi H, West LE, Wen H, Wang EW, et al. Modulation of p53 function by SET8-mediated methylation at lysine 382. Mol Cell. 2007;27:636–46.
Google ScholarÂ
Takawa M, Cho HS, Hayami S, Toyokawa G, Kogure M, Yamane Y, et al. Histone lysine methyltransferase SETD8 promotes carcinogenesis by deregulating PCNA expression. Cancer Res. 2012;72:3217–27.
Google ScholarÂ
Yu B, Su J, Shi Q, Liu Q, Ma J, Ru G, et al. KMT5A-methylated SNIP1 promotes triple-negative breast cancer metastasis by activating YAP signaling. Nat Commun. 2022;13:2192.
Google ScholarÂ
Veschi V, Verona F, Di Bella S, Turdo A, Gaggianesi M, Di Franco S, et al. C1Q(+) TPP1(+) macrophages promote colon cancer progression through SETD8-driven p53 methylation. Mol Cancer. 2025;24:102.
Google ScholarÂ
Yu FX, Zhao B, Guan KL. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell. 2015;163:811–28.
Google ScholarÂ
Zanconato F, Forcato M, Battilana G, Azzolin L, Quaranta E, Bodega B, et al. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nat Cell Biol. 2015;17:1218–27.
Google ScholarÂ
Johnson R, Halder G. The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nat Rev Drug Discov. 2014;13:63–79.
Google ScholarÂ
Kim HB, Kim M, Park YS, Park I, Kim T, Yang SY, et al. Prostaglandin E(2) activates YAP and a positive-signaling loop to promote colon regeneration after colitis but also carcinogenesis in mice. Gastroenterology. 2017;152:616–30.
Google ScholarÂ
Messina B, Lo Sardo F, Scalera S, Memeo L, Colarossi C, Mare M, et al. Hippo pathway dysregulation in gastric cancer: from Helicobacter pylori infection to tumor promotion and progression. Cell Death Dis. 2023;14:21.
Google ScholarÂ
Wang HY, Long QY, Tang SB, Xiao Q, Gao C, Zhao QY, et al. Histone demethylase KDM3A is required for enhancer activation of hippo target genes in colorectal cancer. Nucleic Acids Res. 2019;47:2349–64.
Google ScholarÂ
Heuberger J, Grinat J, Kosel F, Liu L, Kunz S, Vidal RO, et al. High Yap and Mll1 promote a persistent regenerative cell state induced by Notch signaling and loss of p53. Proc Natl Acad Sci USA. 2021;118:e2019425118.
Google ScholarÂ
Fang L, Teng H, Wang Y, Liao G, Weng L, Li Y, et al. SET1A-mediated mono-methylation at K342 regulates YAP activation by blocking its nuclear export and promotes tumorigenesis. Cancer Cell. 2018;34:103–18.e109.
Google ScholarÂ
Gu Y, Chen Y, Wei L, Wu S, Shen K, Liu C, et al. ABHD5 inhibits YAP-induced c-Met overexpression and colon cancer cell stemness via suppressing YAP methylation. Nat Commun. 2021;12:6711.
Google ScholarÂ
Ma A, Yu W, Li F, Bleich RM, Herold JM, Butler KV, et al. Discovery of a selective, substrate-competitive inhibitor of the lysine methyltransferase SETD8. J Med Chem. 2014;57:6822–33.
Google ScholarÂ
Fu J, An L. Histone methylation, energy metabolism, and Alzheimer’s disease. Aging Dis. 2024;16:2831–58.
Google ScholarÂ
Sims RJ 3rd, Nishioka K, Reinberg D. Histone lysine methylation: a signature for chromatin function. Trends Genet. 2003;19:629–39.
Google ScholarÂ
Nishioka K, Rice JC, Sarma K, Erdjument-Bromage H, Werner J, Wang Y, et al. PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin. Mol Cell. 2002;9:1201–13.
Google ScholarÂ
Girish TS, McGinty RK, Tan S. Multivalent interactions by the Set8 histone methyltransferase with its nucleosome substrate. J Mol Biol. 2016;428:1531–43.
Google ScholarÂ
Zhao B, Ye X, Yu J, Li L, Li W, Li S, et al. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev. 2008;22:1962–71.
Google ScholarÂ
Zhang H, Pasolli HA, Fuchs E. Yes-associated protein (YAP) transcriptional coactivator functions in balancing growth and differentiation in skin. Proc Natl Acad Sci USA. 2011;108:2270–5.
Google ScholarÂ
Chan KM, Han J, Fang D, Gan H, Zhang Z. A lesson learned from the H3.3K27M mutation found in pediatric glioma: a new approach to the study of the function of histone modifications in vivo? Cell Cycle. 2013;12:2546–52.
Google ScholarÂ
Fang D, Gan H, Lee JH, Han J, Wang Z, Riester SM, et al. The histone H3.3K36M mutation reprograms the epigenome of chondroblastomas. Science. 2016;352:1344–8.
Google ScholarÂ
Mohammad F, Weissmann S, Leblanc B, Pandey DP, Hojfeldt JW, Comet I, et al. EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas. Nat Med. 2017;23:483–92.
Google ScholarÂ
Jin M, Klionsky DJ. Nuclear proteasomes as a backup for autophagy: interconnected proteostasis pathways. Autophagy. 2025;21:1–2.
Google ScholarÂ
Yang H, Xue M, Su P, Zhou Y, Li X, Li Z, et al. RNF31 represses cell progression and immune evasion via YAP/PD-L1 suppression in triple negative breast cancer. J Exp Clin Cancer Res. 2022;41:364.
Google ScholarÂ
Yokoyama Y, Hieda M, Nishioka Y, Matsumoto A, Higashi S, Kimura H, et al. Cancer-associated upregulation of histone H3 lysine 9 trimethylation promotes cell motility in vitro and drives tumor formation in vivo. Cancer Sci. 2013;104:889–95.
Google ScholarÂ
Peng K, Su G, Ji J, Yang X, Miao M, Mo P, et al. Histone demethylase JMJD1A promotes colorectal cancer growth and metastasis by enhancing Wnt/beta-catenin signaling. J Biol Chem. 2018;293:10606–19.
Google ScholarÂ
Berlin C, Cottard F, Willmann D, Urban S, Tirier SM, Marx L, et al. KMT9 controls stemness and growth of colorectal cancer. Cancer Res. 2022;82:210–20.
Google ScholarÂ
Milite C, Feoli A, Viviano M, Rescigno D, Cianciulli A, Balzano AL, et al. The emerging role of lysine methyltransferase SETD8 in human diseases. Clin Epigenetics. 2016;8:102.
Google ScholarÂ
Zhang X, Peng Y, Yuan Y, Gao Y, Hu F, Wang J, et al. Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells. Cell Death Dis. 2020;11:937.
Google ScholarÂ
Niu L, Kang X, Zheng J, Wu F, Liu S, Hong L, et al. Discovery of KMT5A repressed miR-99b cluster with potential to restore chemotherapy sensitivity in gastric cancer by regulating mitochondrial complex II and affecting OXPHOS. Pharmacol Res. 2025;221:107996.
Google ScholarÂ
Yan S, Zhan F, He Y, Zhu Y, Ma Z. p53 in colorectal cancer: from a master player to a privileged therapy target. J Transl Med. 2025;23:684.
Google ScholarÂ
Mao H, Zhao X, Sun SC. NF-kappaB in inflammation and cancer. Cell Mol Immunol. 2025;22:811–39.
Google ScholarÂ
Murga M, Lopez-Pernas G, Soliva R, Fueyo-Marcos E, Amor C, Faustino I, et al. SETD8 inhibition targets cancer cells with increased rates of ribosome biogenesis. Cell Death Dis. 2024;15:694.
Google ScholarÂ
Cheng C, Su T, Morselli M, Kurdistani SK. Coordinated histone methylation loss and MYC activation promote translational capacity under amino acid restriction. Cancer Metab. 2025;13:29.
Google ScholarÂ
Hirano A, Fu YH, Ptacek LJ. The intricate dance of post-translational modifications in the rhythm of life. Nat Struct Mol Biol. 2016;23:1053–60.
Google ScholarÂ
Meng F, Xie B, Martin JF. Targeting the Hippo pathway in heart repair. Cardiovasc Res. 2022;118:2402–14.
Google ScholarÂ
Biggar KK, Li SS. Non-histone protein methylation as a regulator of cellular signalling and function. Nat Rev Mol Cell Biol. 2015;16:5–17.
Google ScholarÂ
Oudhoff MJ, Freeman SA, Couzens AL, Antignano F, Kuznetsova E, Min PH, et al. Control of the hippo pathway by Set7-dependent methylation of Yap. Dev Cell. 2013;26:188–94.
Google ScholarÂ
Li Z, Su P, Ding Y, Gao H, Yang H, Li X, et al. RBCK1 is an endogenous inhibitor for triple negative breast cancer via hippo/YAP axis. Cell Commun Signal. 2022;20:164.
Google ScholarÂ
Tian Z, Xu C, He W, Lin Z, Zhang W, Tao K, et al. The deubiquitinating enzyme USP19 facilitates hepatocellular carcinoma progression through stabilizing YAP. Cancer Lett. 2023;577:216439.
Google ScholarÂ
Yang W, Han W, Qin A, Wang Z, Xu J, Qian Y. The emerging role of Hippo signaling pathway in regulating osteoclast formation. J Cell Physiol. 2018;233:4606–17.
Google ScholarÂ
Wu Z, Connolly J, Biggar KK. Beyond histones – the expanding roles of protein lysine methylation. FEBS J. 2017;284:2732–44.
Google ScholarÂ
Fang L, Zhang L, Wei W, Jin X, Wang P, Tong Y, et al. A methylation-phosphorylation switch determines Sox2 stability and function in ESC maintenance or differentiation. Mol Cell. 2014;55:537–51.
Google ScholarÂ
Chae YC, Kim JY, Park JW, Kim KB, Oh H, Lee KH, et al. FOXO1 degradation via G9a-mediated methylation promotes cell proliferation in colon cancer. Nucleic Acids Res. 2019;47:1692–705.
Google ScholarÂ
Zhang M, Cai F, Guo J, Liu S, Ma G, Cai M, et al. ACAT2 suppresses the ubiquitination of YAP1 to enhance the proliferation and metastasis ability of gastric cancer via the upregulation of SETD7. Cell Death Dis. 2024;15:297.
Google ScholarÂ
Mazur PK, Reynoird N, Khatri P, Jansen PW, Wilkinson AW, Liu S, et al. SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer. Nature. 2014;510:283–7.
Google ScholarÂ
Liu S, Hausmann S, Carlson SM, Fuentes ME, Francis JW, Pillai R, et al. METTL13 methylation of eEF1A increases translational output to promote tumorigenesis. Cell. 2019;176:491–504.e421.
Google ScholarÂ

