{"title":"通过影响 PI3K/AKT 和 Wnt/β-catenin 信号级联，减少丝氨酸/苏氨酸激酶 39 对急性髓性白血病有抑制肿瘤的作用。","authors":"Chengliang Li , Hong Xin , Jiajia Hao , Yudi Miao","doi":"10.1016/j.taap.2024.116982","DOIUrl":null,"url":null,"abstract":"<div><p>Serine/threonine kinase 39 (STK39) has been identified as a key regulator of tumour progression. However, whether STK39 plays a role in acute myeloid leukaemia (AML) remains undetermined. This work explored the expression and functions of STK39 in AML. STK39 was found to be overexpressed in AML and was negatively correlated with overall survival. Functionally, silencing STK39 inhibited cell proliferation, promoted cell differentiation and induced cell cycle arrest and apoptosis. The tumour inhibiting effects of STK39 downregulation were also verified by an in vivo xenograft tumour assay. Mechanistically, STK39 was closely related to the PI3K/AKT and Wnt/β-catenin signalling cascades in AML. Silencing of STK39 had suppressive effects on the PI3K/AKT and Wnt/β-catenin signalling cascades. The suppressive effect of STK39 silencing on the Wnt/β-catenin signalling cascade was significantly reversed when PI3K/AKT was reactivated. When β-catenin was re-expressed, the tumour-inhibiting effects caused by STK39 silencing were significantly eliminated. Therefore, STK39 plays a crucial role in AML and could be targeted for potential therapeutic purposes in treating AML.</p></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Decreasing of serine/threonine kinase 39 has tumour inhibiting effects on acute myeloid leukaemia by impacting the PI3K/AKT and Wnt/β-catenin signalling cascades\",\"authors\":\"Chengliang Li , Hong Xin , Jiajia Hao , Yudi Miao\",\"doi\":\"10.1016/j.taap.2024.116982\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Serine/threonine kinase 39 (STK39) has been identified as a key regulator of tumour progression. However, whether STK39 plays a role in acute myeloid leukaemia (AML) remains undetermined. This work explored the expression and functions of STK39 in AML. STK39 was found to be overexpressed in AML and was negatively correlated with overall survival. Functionally, silencing STK39 inhibited cell proliferation, promoted cell differentiation and induced cell cycle arrest and apoptosis. The tumour inhibiting effects of STK39 downregulation were also verified by an in vivo xenograft tumour assay. Mechanistically, STK39 was closely related to the PI3K/AKT and Wnt/β-catenin signalling cascades in AML. Silencing of STK39 had suppressive effects on the PI3K/AKT and Wnt/β-catenin signalling cascades. The suppressive effect of STK39 silencing on the Wnt/β-catenin signalling cascade was significantly reversed when PI3K/AKT was reactivated. When β-catenin was re-expressed, the tumour-inhibiting effects caused by STK39 silencing were significantly eliminated. Therefore, STK39 plays a crucial role in AML and could be targeted for potential therapeutic purposes in treating AML.</p></div>\",\"PeriodicalId\":23174,\"journal\":{\"name\":\"Toxicology and applied pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-05-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicology and applied pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0041008X24001807\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology and applied pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0041008X24001807","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Decreasing of serine/threonine kinase 39 has tumour inhibiting effects on acute myeloid leukaemia by impacting the PI3K/AKT and Wnt/β-catenin signalling cascades
Serine/threonine kinase 39 (STK39) has been identified as a key regulator of tumour progression. However, whether STK39 plays a role in acute myeloid leukaemia (AML) remains undetermined. This work explored the expression and functions of STK39 in AML. STK39 was found to be overexpressed in AML and was negatively correlated with overall survival. Functionally, silencing STK39 inhibited cell proliferation, promoted cell differentiation and induced cell cycle arrest and apoptosis. The tumour inhibiting effects of STK39 downregulation were also verified by an in vivo xenograft tumour assay. Mechanistically, STK39 was closely related to the PI3K/AKT and Wnt/β-catenin signalling cascades in AML. Silencing of STK39 had suppressive effects on the PI3K/AKT and Wnt/β-catenin signalling cascades. The suppressive effect of STK39 silencing on the Wnt/β-catenin signalling cascade was significantly reversed when PI3K/AKT was reactivated. When β-catenin was re-expressed, the tumour-inhibiting effects caused by STK39 silencing were significantly eliminated. Therefore, STK39 plays a crucial role in AML and could be targeted for potential therapeutic purposes in treating AML.
期刊介绍：
Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products.
Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged.
Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.
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