Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
June-2025 Volume 29 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2025 Volume 29 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Role of SMYD2 in gastrointestinal cancer progression (Review)

  • Authors:
    • Kun Xia
    • Yaoxiang Zhou
    • Youping Xie
    • Yinzhong Cai
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, People's Hospital of Ningxiang City, Ningxiang, Hunan 410600, P.R. China
    Copyright: © Xia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 282
    |
    Published online on: April 8, 2025
       https://doi.org/10.3892/ol.2025.15028
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:


Abstract

Gastrointestinal cancer is one of the most prevalent malignancies in humans and is often associated with a poor prognosis. Understanding the molecular mechanisms underlying cancer progression and severity is essential for the development of effective cancer therapies. Abnormal protein methylation is associated with the occurrence and advancement of cancer, highlighting the importance of protein methyltransferase research. SET and MYND domain‑containing protein 2 (SMYD2), a lysine methyltransferase, has emerged as a promising small molecule target for cancer treatment. Notably, SMYD2 is implicated in the pathogenesis of several diseases, including gastrointestinal cancer. SMYD2 is closely associated with the tumorigenesis, proliferation, migration and other biological processes of gastrointestinal cancer, indicating its potential as a novel therapeutic target. The present review offers an in‑depth analysis of SMYD2, covering its structural characteristics, regulatory pathways and functional significance. By assessing the biological roles and therapeutic potential of SMYD2, the current review presents fresh insights and perspectives for advancing research in different types of gastrointestinal cancer.
View Figures

Figure 1

Figure 2

View References

1 

Arnold M, Abnet CC, Neale RE, Vignat J, Giovannucci EL, McGlynn KA and Bray F: Global burden of 5 major types of gastrointestinal cancer. Gastroenterology. 159:335–349.e15. 2020. View Article : Google Scholar : PubMed/NCBI

2 

Zhang FF, Luo YH, Wang H and Zhao L: Metastasis-associated long noncoding RNAs in gastrointestinal cancer: Implications for novel biomarkers and therapeutic targets. World J Gastroenterol. 22:8735–8749. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Grady WM: Epigenetic alterations in the gastrointestinal tract: Current and emerging use for biomarkers of cancer. Adv Cancer Res. 151:425–468. 2021. View Article : Google Scholar : PubMed/NCBI

4 

Wang DK, Zuo Q, He QY and Li B: Targeted immunotherapies in gastrointestinal cancer: From molecular mechanisms to implications. Front Immunol. 12:7059992021. View Article : Google Scholar : PubMed/NCBI

5 

Cao Z, Shu Y, Wang J, Wang C, Feng T, Yang L, Shao J and Zou L: Super enhancers: Pathogenic roles and potential therapeutic targets for acute myeloid leukemia (AML). Genes Dis. 9:1466–1477. 2022. View Article : Google Scholar : PubMed/NCBI

6 

Brown MA, Sims RJ III, Gottlieb PD and Tucker PW: Identification and characterization of Smyd2: A split SET/MYND domain-containing histone H3 lysine 36-specific methyltransferase that interacts with the Sin3 histone deacetylase complex. Mol Cancer. 5:262006. View Article : Google Scholar : PubMed/NCBI

7 

Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, Kubicek S, Opravil S, Jenuwein T and Berger SL: Repression of p53 activity by Smyd2-mediated methylation. Nature. 444:629–632. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Zeng Y, Qiu R, Yang Y, Gao T, Zheng Y, Huang W, Gao J, Zhang K, Liu R, Wang S, et al: Regulation of EZH2 by SMYD2-mediated lysine methylation is implicated in tumorigenesis. Cell Rep. 29:1482–1498.e4. 2019. View Article : Google Scholar : PubMed/NCBI

9 

Sajjad A, Novoyatleva T, Vergarajauregui S, Troidl C, Schermuly RT, Tucker HO and Engel FB: Lysine methyltransferase Smyd2 suppresses p53-dependent cardiomyocyte apoptosis. Biochim Biophys Acta. 1843:2556–2562. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Komatsu S, Ichikawa D, Hirajima S, Nagata H, Nishimura Y, Kawaguchi T, Miyamae M, Okajima W, Ohashi T, Konishi H, et al: Overexpression of SMYD2 contributes to malignant outcome in gastric cancer. Br J Cancer. 112:357–364. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Hamamoto R, Toyokawa G, Nakakido M, Ueda K and Nakamura Y: SMYD2-dependent HSP90 methylation promotes cancer cell proliferation by regulating the chaperone complex formation. Cancer Lett. 351:126–133. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Reynoird N, Mazur PK, Stellfeld T, Flores NM, Lofgren SM, Carlson SM, Brambilla E, Hainaut P, Kaznowska EB, Arrowsmith CH, et al: Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer. Genes Dev. 30:772–785. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Eggert E, Hillig RC, Koehr S, Stöckigt D, Weiske J, Barak N, Mowat J, Brumby T, Christ CD, Ter Laak A, et al: Discovery and characterization of a highly potent and selective aminopyrazoline-based in vivo probe (BAY-598) for the protein lysine methyltransferase SMYD2. J Med Chem. 59:4578–4600. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Hamamoto R, Saloura V and Nakamura Y: Critical roles of non-histone protein lysine methylation in human tumorigenesis. Nat Rev Cancer. 15:110–124. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Zheng Q, Zhang W and Rao GW: Protein lysine methyltransferase SMYD2: A promising small molecule target for cancer therapy. J Med Chem. 65:10119–10132. 2022. View Article : Google Scholar : PubMed/NCBI

16 

Copeland RA: Protein methyltransferase inhibitors as precision cancer therapeutics: A decade of discovery. Philos Trans R Soc Lond B Biol Sci. 373:201700802018. View Article : Google Scholar : PubMed/NCBI

17 

Copeland RA: Epigenetic medicinal chemistry. ACS Med Chem Lett. 7:124–127. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Tang M, Chen G, Tu B, Hu Z, Huang Y, DuFort CC, Wan X, Mao Z, Liu Y, Zhu WG and Lu W: SMYD2 inhibition-mediated hypomethylation of Ku70 contributes to impaired nonhomologous end joining repair and antitumor immunity. Sci Adv. 9:eade66242023. View Article : Google Scholar : PubMed/NCBI

19 

Meng J, Yang W, Li C and Li F: Synergistic anticancer effects of SMYD2 inhibitor BAY-598 and doxorubicin in non-small cell lung cancer. Heliyon. 10:e320152024. View Article : Google Scholar : PubMed/NCBI

20 

Razmi M, Yazdanpanah A, Etemad-Moghadam S, Alaeddini M, Angelini S and Eini L: Clinical prognostic value of the SMYD2/3 as new epigenetic biomarkers in solid cancer patients: A systematic review and meta-analysis. Expert Rev Mol Diagn. 1–15. 2022.(Epub ahead of print). PubMed/NCBI

21 

Rubio-Tomás T: Novel insights into SMYD2 and SMYD3 inhibitors: From potential anti-tumoural therapy to a variety of new applications. Mol Biol Rep. 48:7499–7508. 2021. View Article : Google Scholar : PubMed/NCBI

22 

Liu D, Yang X and Wang X: Neutrophil extracellular traps promote gastric cancer cell metastasis via the NAT10-mediated N4-acetylcytidine modification of SMYD2. Cell Signal. 116:1110142024. View Article : Google Scholar : PubMed/NCBI

23 

Carr SR, Akerley W, Hashibe M and Cannon-Albright LA: Evidence for a genetical contribution to non-smoking-related lung cancer. Thorax. 70:1033–1039. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Spellmon N, Holcomb J, Trescott L, Sirinupong N and Yang Z: Structure and function of SET and MYND domain-containing proteins. Int J Mol Sci. 16:1406–1428. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Leinhart K and Brown M: SET/MYND lysine methyltransferases regulate gene transcription and protein activity. Genes (Basel). 2:210–218. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Ferguson AD, Larsen NA, Howard T, Pollard H, Green I, Grande C, Cheung T, Garcia-Arenas R, Cowen S, Wu J, et al: Structural basis of substrate methylation and inhibition of SMYD2. Structure. 19:1262–1273. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Xu S, Zhong C, Zhang T and Ding J: Structure of human lysine methyltransferase Smyd2 reveals insights into the substrate divergence in Smyd proteins. J Mol Cell Biol. 3:293–300. 2011. View Article : Google Scholar : PubMed/NCBI

28 

‘SMYD2-SET and MYND domain-containing protein 2’. UniProt; Geneva: 2024, https://www.uniprot.org/uniprot/Q9NRG4

29 

Herz HM, Garruss A and Shilatifard A: SET for life: Biochemical activities and biological functions of SET domain-containing proteins. Trends Biochem Sci. 38:621–639. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Wu J, Cheung T, Grande C, Ferguson AD, Zhu X, Theriault K, Code E, Birr C, Keen N and Chen H: Biochemical characterization of human SET and MYND domain-containing protein 2 methyltransferase. Biochemistry. 50:6488–6497. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Abu-Farha M, Lambert JP, Al-Madhoun AS, Elisma F, Skerjanc IS and Figeys D: The tale of two domains: Proteomics and genomics analysis of SMYD2, a new histone methyltransferase. Mol Cell Proteomics. 7:560–572. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Spellmon N, Sun X, Sirinupong N, Edwards B, Li C and Yang Z: Molecular dynamics simulation reveals correlated inter-lobe motion in protein lysine methyltransferase SMYD2. PLoS One. 10:e01457582015. View Article : Google Scholar : PubMed/NCBI

33 

Xu S, Wu J, Sun B, Zhong C and 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. 39:4438–4449. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Sirinupong N, Brunzelle J, Ye J, Pirzada A, Nico L and Yang Z: Crystal structure of cardiac-specific histone methyltransferase SmyD1 reveals unusual active site architecture. J Biol Chem. 285:40635–40644. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Chandramouli B and Chillemi G: Conformational dynamics of lysine methyltransferase Smyd2. insights into the different substrate crevice characteristics of Smyd2 and Smyd3. J Chem Inf Model. 56:2467–2475. 2016. View Article : Google Scholar : PubMed/NCBI

36 

Zhang Y, Alshammari E, Sobota J, Spellmon N, Perry E, Cao T, Mugunamalwaththa T, Smith S, Brunzelle J, Wu G, et al: Structure of the SMYD2-PARP1 complex reveals both productive and allosteric modes of peptide binding. bioRxiv [Preprint]. 2024.12.03.626679. 2024.

37 

Gottlieb PD, Pierce SA, Sims RJ, Yamagishi H, Weihe EK, Harriss JV, Maika SD, Kuziel WA, King HL, Olson EN, et al: Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis. Nat Genet. 31:25–32. 2002. View Article : Google Scholar : PubMed/NCBI

38 

Sesé B, Barrero MJ, Fabregat MC, Sander V and Izpisua Belmonte JC: SMYD2 is induced during cell differentiation and participates in early development. Int J Dev Biol. 57:357–364. 2013. View Article : Google Scholar : PubMed/NCBI

39 

Diehl F, Brown MA, van Amerongen MJ, Novoyatleva T, Wietelmann A, Harriss J, Ferrazzi F, Böttger T, Harvey RP, Tucker PW and Engel FB: Cardiac deletion of Smyd2 is dispensable for mouse heart development. PLoS One. 5:e97482010. View Article : Google Scholar : PubMed/NCBI

40 

Kawamura S, Yoshigai E, Kuhara S and Tashiro K: smyd1 and smyd2 are expressed in muscle tissue in Xenopus laevis. Cytotechnology. 57:161–168. 2008. View Article : Google Scholar : PubMed/NCBI

41 

Alshammari E, Zhang YX and Yang Z: Mechanistic and functional extrapolation of SET and MYND domain-containing protein 2 to pancreatic cancer. World J Gastroenterol. 28:3753–3766. 2022. View Article : Google Scholar : PubMed/NCBI

42 

Boehm D, Jeng M, Camus G, Gramatica A, Schwarzer R, Johnson JR, Hull PA, Montan M, Sakane N, Pagans S, et al: SMYD2-mediated histone methylation contributes to HIV-1 latency. Cell Host Microbe. 21:569–579.e6. 2017. View Article : Google Scholar : PubMed/NCBI

43 

Olsen JB, Cao XJ, Han B, Chen LH, Horvath A, Richardson TI, Campbell RM, Garcia BA and Nguyen H: Quantitative profiling of the activity of protein lysine methyltransferase SMYD2 using SILAC-based proteomics. Mol Cell Proteomics. 15:892–905. 2016. View Article : Google Scholar : PubMed/NCBI

44 

Weirich S, Schuhmacher MK, Kudithipudi S, Lungu C, Ferguson AD and Jeltsch A: Analysis of the substrate specificity of the SMYD2 protein lysine methyltransferase and discovery of novel non-histone substrates. Chembiochem. 21:256–264. 2020. View Article : Google Scholar : PubMed/NCBI

45 

Li LX, Fan LX, Zhou JX, Grantham JJ, Calvet JP, Sage J and Li X: Lysine methyltransferase SMYD2 promotes cyst growth in autosomal dominant polycystic kidney disease. J Clin Invest. 127:2751–2764. 2017. View Article : Google Scholar : PubMed/NCBI

46 

Piao L, Kang D, Suzuki T, Masuda A, Dohmae N, Nakamura Y and Hamamoto R: The histone methyltransferase SMYD2 methylates PARP1 and promotes poly(ADP-ribosyl)ation activity in cancer cells. Neoplasia. 16:257–264. 264.e22014. View Article : Google Scholar : PubMed/NCBI

47 

Nakakido M, Deng Z, Suzuki T, Dohmae N, Nakamura Y and Hamamoto R: Dysregulation of AKT pathway by SMYD2-mediated lysine methylation on PTEN. Neoplasia. 17:367–373. 2015. View Article : Google Scholar : PubMed/NCBI

48 

Saddic LA, West LE, Aslanian A, Yates JR III, Rubin SM, Gozani O and Sage J: Methylation of the retinoblastoma tumor suppressor by SMYD2. J Biol Chem. 285:37733–37740. 2010. View Article : Google Scholar : PubMed/NCBI

49 

Cho HS, Hayami S, Toyokawa G, Maejima K, Yamane Y, Suzuki T, Dohmae N, Kogure M, Kang D, Neal DE, et al: RB1 methylation by SMYD2 enhances cell cycle progression through an increase of RB1 phosphorylation. Neoplasia. 14:476–486. 2012. View Article : Google Scholar : PubMed/NCBI

50 

Obermann WMJ: A motif in HSP90 and P23 that links molecular chaperones to efficient estrogen receptor α methylation by the lysine methyltransferase SMYD2. J Biol Chem. 293:16479–16487. 2018. View Article : Google Scholar : PubMed/NCBI

51 

Ji K, Jia H, Liu Z, Yu G, Wen R, Zhang T, Peng Z, Man W, Tian Y, Wang C, et al: New insight in immunotherapy and combine therapy in colorectal cancer. Front Cell Dev Biol. 12:14536302025. View Article : Google Scholar : PubMed/NCBI

52 

Meng F, Liu X, Lin C, Xu L, Liu J, Zhang P, Zhang X, Song J, Yan Y, Ren Z and Zhang Y: SMYD2 suppresses APC2 expression to activate the Wnt/β-catenin pathway and promotes epithelial-mesenchymal transition in colorectal cancer. Am J Cancer Res. 10:997–1011. 2020.PubMed/NCBI

53 

Yu YQ, Thonn V, Patankar JV, Thoma OM, Waldner M, Zielinska M, Bao LL, Gonzalez-Acera M, Wallmüller S, Engel FB, et al: SMYD2 targets RIPK1 and restricts TNF-induced apoptosis and necroptosis to support colon tumor growth. Cell Death Dis. 13:522022. View Article : Google Scholar : PubMed/NCBI

54 

Zhang Y, Zhou L, Xu Y, Zhou J, Jiang T, Wang J, Li C, Sun X, Song H and Song J: Targeting SMYD2 inhibits angiogenesis and increases the efficiency of apatinib by suppressing EGFL7 in colorectal cancer. Angiogenesis. 26:1–18. 2023. View Article : Google Scholar : PubMed/NCBI

55 

Lai Y and Yang Y: SMYD2 facilitates cancer cell malignancy and xenograft tumor development through ERBB2-mediated FUT4 expression in colon cancer. Mol Cell Biochem. 477:2149–2159. 2022. View Article : Google Scholar : PubMed/NCBI

56 

Ren H, Wang Z, Chen Y, Liu Y, Zhang S, Zhang T and Li Y: SMYD2-OE promotes oxaliplatin resistance in colon cancer through MDR1/P-glycoprotein via MEK/ERK/AP1 pathway. Onco Targets Ther. 12:2585–2594. 2019. View Article : Google Scholar : PubMed/NCBI

57 

Yue M, Liu T, Yan G, Luo X and Wang L: LINC01605, regulated by the EP300-SMYD2 complex, potentiates the binding between METTL3 and SPTBN2 in colorectal cancer. Cancer Cell Int. 21:5042021. View Article : Google Scholar : PubMed/NCBI

58 

Pan L, Fan Y and Zhou L: SMYD2 epigenetically activates MEX3A and suppresses CDX2 in colorectal cancer cells to augment cancer growth. Clin Exp Pharmacol Physiol. 49:959–969. 2022. View Article : Google Scholar : PubMed/NCBI

59 

Deng X, Hamamoto R, Vougiouklakis T, Wang R, Yoshioka Y, Suzuki T, Dohmae N, Matsuo Y, Park JH and Nakamura Y: Critical roles of SMYD2-mediated β-catenin methylation for nuclear translocation and activation of Wnt signaling. Oncotarget. 8:55837–55847. 2027. View Article : Google Scholar : PubMed/NCBI

60 

Ma X, Xu W, Qi L, Zhang Q, Sun X and Zhang S: Clinical outcome of non-curative endoscopic submucosal dissection for early gastric cancer. J Gastrointest Oncol. 15:566–576. 2024. View Article : Google Scholar : PubMed/NCBI

61 

Liu Z, Xu H, You W, Pan K and Li W: Helicobacter pylori eradication for primary prevention of gastric cancer: Progresses and challenges. J Natl Cancer Cent. 4:299–310. 2024. View Article : Google Scholar : PubMed/NCBI

62 

Liu D, Liu M, Wang W, Li X, Shi E, Zhang C, Wang Y, Zhang Y, Wang L and Wang X: SMYD family members serve as potential prognostic markers and correlate with immune infiltrates in gastric cancer. J Oncol. 2023:60328642023. View Article : Google Scholar : PubMed/NCBI

63 

Liu D, Wang X, Shi E, Wang L, Nie M, Li L, Jiang Q, Kong P, Shi S, Wang C, et al: Comprehensive analysis of the value of SMYD family members in the prognosis and immune infiltration of malignant digestive system tumors. Front Genet. 12:6999102021. View Article : Google Scholar : PubMed/NCBI

64 

Xu H, Ba Z, Liu C and Yu X: Long noncoding RNA DLEU1 promotes proliferation and glycolysis of gastric cancer cells via APOC1 upregulation by recruiting SMYD2 to induce trimethylation of H3K4 modification. Transl Oncol. 36:1017312023. View Article : Google Scholar : PubMed/NCBI

65 

He C, Wang Z, Yu J, Mao S and Xiang X: Current drug resistance mechanisms and treatment options in gastrointestinal stromal tumors: Summary and update. Curr Treat Options Oncol. 25:1390–1405. 2024. View Article : Google Scholar : PubMed/NCBI

66 

Ji Y, Xu X, Long C, Wang J, Ding L, Zheng Z, Wu H, Yang L, Tao L and Gao F: SMYD2 aggravates gastrointestinal stromal tumor via upregulation of EZH2 and downregulation of TET1. Cell Death Discov. 8:2742022. View Article : Google Scholar : PubMed/NCBI

67 

Yu Y, Qi J, Xiong J, Jiang L, Cui D, He J, Chen P, Li L, Wu C, Ma T, et al: Epigenetic co-deregulation of EZH2/TET1 is a senescence-countering, actionable vulnerability in triple-negative breast cancer. Theranostics. 9:761–777. 2019. View Article : Google Scholar : PubMed/NCBI

68 

Hwang SY, Danpanichkul P, Agopian V, Mehta N, Parikh ND, Abou-Alfa GK, Singal AG and Yang JD: Hepatocellular carcinoma: Updates on epidemiology, surveillance, diagnosis and treatment. Clin Mol Hepatol. 31 (Suppl):S228–S254. 2025. View Article : Google Scholar : PubMed/NCBI

69 

Zuo SR, Zuo XC, He Y, Fang WJ, Wang CJ, Zou H, Chen P, Huang LF, Huang LH, Xiang H and Liu SK: Positive expression of SMYD2 is associated with poor prognosis in patients with primary hepatocellular carcinoma. J Cancer. 9:321–330. 2018. View Article : Google Scholar : PubMed/NCBI

70 

Fang W, Song L, Li Z, Meng P, Zuo S and Liu S: Effect of miRNA-200b on the proliferation of liver cancer cells via targeting SMYD2/p53 signaling pathway. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 47:1303–1314. 2022.(In English, Chinese). PubMed/NCBI

71 

Xu K, Ding J, Zhou L, Li D, Luo J, Wang W, Shang M, Lin B, Zhou L and Zheng S: SMYD2 promotes hepatocellular carcinoma progression by reprogramming glutamine metabolism via c-Myc/GLS1 axis. Cells. 12:252022. View Article : Google Scholar : PubMed/NCBI

72 

Liu R, Guo Y, Wang L, Yin G, Tuo H, Zhu Y, Yang W, Liu Q and Wang Y: A novel hypoxia-induced lncRNA, SZT2-AS1, boosts HCC progression by mediating HIF heterodimerization and histone trimethylation under a hypoxic microenvironment. Cell Death Differ. Nov 22–2024.(Epub ahead of print).

73 

Jiang Z, Zheng X, Li M and Liu M: Improving the prognosis of pancreatic cancer: Insights from epidemiology, genomic alterations, and therapeutic challenges. Front Med. 17:1135–1169. 2023. View Article : Google Scholar : PubMed/NCBI

74 

Tan J, Liao S, Yuan B, Liu X, Yu W, Zhan H, Jiang Y and Liu Y: Targeting SMYD2 promotes ferroptosis and impacts the progression of pancreatic cancer through the c-Myc/NCOA4 axis-mediated ferritinophagy. Biochim Biophys Acta Gen Subj. 1868:1306832024. View Article : Google Scholar : PubMed/NCBI

75 

Mancias JD, Wang X, Gygi SP, Harper JW and Kimmelman AC: Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature. 509:105–109. 2014. View Article : Google Scholar : PubMed/NCBI

76 

Jin Y, Qiu J, Lu X and Li G: C-MYC inhibited ferroptosis and promoted immune evasion in ovarian cancer cells through NCOA4 mediated ferritin autophagy. Cells. 11:41272022. View Article : Google Scholar : PubMed/NCBI

77 

Lenkiewicz E, Malasi S, Hogenson TL, Flores LF, Barham W, Phillips WJ, Roesler AS, Chambers KR, Rajbhandari N, Hayashi A, et al: Genomic and epigenomic landscaping defines new therapeutic targets for adenosquamous carcinoma of the pancreas. Cancer Res. 80:4324–4334. 2020. View Article : Google Scholar : PubMed/NCBI

78 

Zhao Q, Ye Y, Zhang Q, Wu Y, Wang G, Gui Z and Zhang M: PANoptosis-related long non-coding RNA signature to predict the prognosis and immune landscapes of pancreatic adenocarcinoma. Biochem Biophys Rep. 37:1016002023.PubMed/NCBI

79 

Xu Z, Liu Y, Pan Z and Qin L: Epigenetic upregulation of MNAT1 by SMYD2 is linked to PI3K/AKT activation and tumorigenesis of pancreatic adenocarcinoma. Histol Histopathol. 39:263–277. 2024.PubMed/NCBI

80 

Jin L, Qian D, Tang X, Huang Y, Zou J and Wu Z: SMYD2 imparts gemcitabine resistance to pancreatic adenocarcinoma cells by upregulating EVI2A. Mol Biotechnol. 66:2920–2933. 2024. View Article : Google Scholar : PubMed/NCBI

81 

Jiang W, Zhang B, Xu J, Xue L and Wang L: Current status and perspectives of esophageal cancer: A comprehensive review. Cancer Commun (Lond). 45:281–331. 2025. View Article : Google Scholar : PubMed/NCBI

82 

Komatsu S, Imoto I, Tsuda H, Kozaki KI, Muramatsu T, Shimada Y, Aiko S, Yoshizumi Y, Ichikawa D, Otsuji E and Inazawa J: Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous cell carcinoma. Carcinogenesis. 30:1139–1146. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xia K, Zhou Y, Xie Y and Cai Y: Role of SMYD2 in gastrointestinal cancer progression (Review). Oncol Lett 29: 282, 2025.
APA
Xia, K., Zhou, Y., Xie, Y., & Cai, Y. (2025). Role of SMYD2 in gastrointestinal cancer progression (Review). Oncology Letters, 29, 282. https://doi.org/10.3892/ol.2025.15028
MLA
Xia, K., Zhou, Y., Xie, Y., Cai, Y."Role of SMYD2 in gastrointestinal cancer progression (Review)". Oncology Letters 29.6 (2025): 282.
Chicago
Xia, K., Zhou, Y., Xie, Y., Cai, Y."Role of SMYD2 in gastrointestinal cancer progression (Review)". Oncology Letters 29, no. 6 (2025): 282. https://doi.org/10.3892/ol.2025.15028
Copy and paste a formatted citation
x
Spandidos Publications style
Xia K, Zhou Y, Xie Y and Cai Y: Role of SMYD2 in gastrointestinal cancer progression (Review). Oncol Lett 29: 282, 2025.
APA
Xia, K., Zhou, Y., Xie, Y., & Cai, Y. (2025). Role of SMYD2 in gastrointestinal cancer progression (Review). Oncology Letters, 29, 282. https://doi.org/10.3892/ol.2025.15028
MLA
Xia, K., Zhou, Y., Xie, Y., Cai, Y."Role of SMYD2 in gastrointestinal cancer progression (Review)". Oncology Letters 29.6 (2025): 282.
Chicago
Xia, K., Zhou, Y., Xie, Y., Cai, Y."Role of SMYD2 in gastrointestinal cancer progression (Review)". Oncology Letters 29, no. 6 (2025): 282. https://doi.org/10.3892/ol.2025.15028
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team