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This review focuses on the SET and MYND domain-containing protein (SMYD) family, describing how SMYD members control cancer-related gene regulation through histone and nonhistone methylation. The article highlights SMYD roles in regulating oncogene and tumor suppressor expression, predicting prognosis, and influencing chemotherapy resistance. It also discusses therapeutic potential, such as developing SMYD-targeted inhibitors and combining them with anticancer agents.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/smyd-family-in-cancer-epigenetic-regulation-and-molecular-mechanisms-of-cancer-proliferation-metastasis-and-drug-resistance/337100/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/smyd-family-in-cancer-epigenetic-regulation-and-molecular-mechanisms-of-cancer-proliferation-metastasis-and-drug-resistance/337100.png","ImageObject",300,407,{"name":92,"@type":93},"Evangeline","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What epigenetic processes are emphasized as important in cancer development?","Question",{"text":112,"@type":113},"The article highlights DNA methylation, histone modifications (methylation, acetylation, phosphorylation, ubiquitylation), and microRNAs as key regulators of oncogene and tumor suppressor gene expression during cancer growth.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which proteins belong to the SMYD family discussed in the review?",{"text":117,"@type":113},"The review describes SMYD1, SMYD2, SMYD3, SMYD4, and SMYD5, which share SET and MYND domains and regulate methylation of histone H3 lysines as well as nonhistone substrates.",{"name":119,"@type":110,"acceptedAnswer":120},"How might targeting SMYD family members contribute to cancer therapy?",{"text":121,"@type":113},"Because SMYD proteins contribute to proliferation, metastasis, prognosis, and drug resistance, the review suggests that developing inhibitors against specific SMYD family members could support cancer treatment, potentially improved by combination therapy with other anticancer agents.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},337100,1790119542,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41},13056703019662,"https://ap-avatar.wpscdn.com/avatar/be000253a8e92610077?_k=1778726343310543188","[www.nature.com/emm](www.nature.com/emm)  \nREVIEW ARTICLE OPEN   \nSMYD family in cancer: epigenetic regulation and molecular mechanisms of cancer proliferation, metastasis, and drug resistance  \nTae-Su Han 1,2,3, Dae-Soo Kim 1,2 ✉, Mi-Young Son 1,2,3 ✉ and Hyun-Soo Cho 1,2,3 ✉  \n© The Author(s) 2024  \n|  |  |  |\n| --- | --- | --- |\n|  | Epigenetic modifiers (miRNAs, histone methyltransferases (HMTs)/demethylases, and DNA methyltransferases/demethylases) are associated with cancer proliferation, metastasis, angiogenesis, and drug resistance. Among these modifiers, HMTs are frequently overexpressed in various cancers, and recent studies have increasingly identified these proteins as potential therapeutic targets. In this review, we discuss members of the SET and MYND domain-containing protein (SMYD) family that are topics of extensive research on the histone methylation and nonhistone methylation of cancer-related genes. Various members of the SMYD family play significant roles in cancer proliferation, metastasis, and drug resistance by regulating cancer-specific histone methylation and nonhistone methylation. Thus, the development of specific inhibitors that target SMYD family members may lead to the development of cancer treatments, and combination therapy with various anticancer therapeutic agents may increase treatment |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| efficacy. |  |  |\n|  | Experimental & Molecular Medicine (2024) 56:2325–2336; [https://doi.org/10.1038/s12276-024-01326-8](https://doi.org/10.1038/s12276-024-01326-8) |  |\n|  |  |  |\n\nINTRODUCTION  \nEpigenetic processes play crucial roles in various stages of cancer growth. DNA methylation, histone modification (including methylation, acetylation, phosphorylation, and ubiquitylation), and microRNAs (miRNAs) are associated with the regulation of oncogene and tumor suppressor gene expression1–4. Recently, through public databases such as The Cancer Genome Atlas (TCGA) database, it has been observed that the expression levels of epigenetic modifiers are up- or downregulated in cancer cells, suggesting their involvement in cancer-related processes5–7.  \nAmong epigenetic modifiers, histone methyltransferases (HMTs), which are responsible for histone methylation in cancerrelated epigenetic processes, are involved in regulating the expression of various oncogenes and tumor suppressor genes by altering euchromatin and heterochromatin structures8. Consequently, the expression of genes related to cancer growth, metastasis, and chemotherapy resistance is regulated by HMTs, making these enzymes potential therapeutic targets for cancer treatment9. In recent developments in cancer therapy, specific inhibitors, such as tazemetostat, which targets enhancer of zeste homolog 2 (EZH2) and thereby mediates histone H3 lysine (K) 27 methylation, have been approved by the Food and Drug Administration (FDA) for the treatment of follicular lymphoma and are currently in use. Moreover, various clinical studies are being conducted to explore the possibility of applying these inhibitors to treat different cancers10. The successful development of EZH2 inhibitors has led to active research on the mechanisms by which various HMTs function, and these studies have shown  \nthat HMTs have potential for use as crucial targets for cancer treatment.  \nTherefore, the aim of this review was to describe the SET and MYND domain-containing protein (SMYD) family, which has recently been reported to be associated with cancer growth, metastasis, and chemotherapy resistance. This review also aims to determine the potential of SMYD family members as therapeutic targets for cancer treatment.  \nSMYD FAMILY MEMBERS  \nThe SMYD family includes SMYD1, SMYD2, SMYD3, SMYD4, and SMYD5, which are responsible for the monomethylation of histone H3 lysine (K) 4 and the dimethylation of H3K3611. The SMYD family shares a similar structure. All members of the SMYD family commonly possess the","cbCaiumoshsIfan9","https://ap.wps.com/l/cbCaiumoshsIfan9","pdf",2039611,12,"English","# Introduction\n# SMYD family members","[{\"question\":\"What epigenetic processes are emphasized as important in cancer development?\",\"answer\":\"The article highlights DNA methylation, histone modifications (methylation, acetylation, phosphorylation, ubiquitylation), and microRNAs as key regulators of oncogene and tumor suppressor gene expression during cancer growth.\"},{\"question\":\"Which proteins belong to the SMYD family discussed in the review?\",\"answer\":\"The review describes SMYD1, SMYD2, SMYD3, SMYD4, and SMYD5, which share SET and MYND domains and regulate methylation of histone H3 lysines as well as nonhistone substrates.\"},{\"question\":\"How might targeting SMYD family members contribute to cancer therapy?\",\"answer\":\"Because SMYD proteins contribute to proliferation, metastasis, prognosis, and drug resistance, the review suggests that developing inhibitors against specific SMYD family members could support cancer treatment, potentially improved by combination therapy with other anticancer agents.\"}]","SMYD family in cancer - epigenetic regulation and molecular mechanisms of cancer proliferation, metastasis, and drug resistance | PDF",1790017689]