Xu Cao, Jinhai Tian, Man Yee Cheung, Liangying Zhang, Zimei Liu, Zongying Jiang, Shaoting Zhang, Kun Xiao, Sien Zhao, Ming Wang, Feng Ding, Shujing Li, Lijun Ma, Hui Zhao, Jianmin Sun
{"title":"ZSWIM4 进入细胞核是其抑制胃肠道间质瘤中 KIT 和 BMAL1 的关键。","authors":"Xu Cao, Jinhai Tian, Man Yee Cheung, Liangying Zhang, Zimei Liu, Zongying Jiang, Shaoting Zhang, Kun Xiao, Sien Zhao, Ming Wang, Feng Ding, Shujing Li, Lijun Ma, Hui Zhao, Jianmin Sun","doi":"10.1186/s13578-024-01271-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Zinc finger SWIM-type containing 4 (ZSWIM4) is a zinc finger protein with its function largely uncharacterized. In this study, we aimed to investigate the role of ZSWIM4 in gastrointestinal stromal tumors (GISTs).</p><p><strong>Results: </strong>We found that ZSWIM4 expression is inhibited by the predominantly mutated protein KIT in GISTs, while conversely, ZSWIM4 inhibits KIT expression and downstream signaling. Consistent with the observation, ZSWIM4 inhibited GIST cell survival and proliferation in vitro. RNA sequencing of GISTs from KIT<sup>V558A/WT</sup> mice and KIT<sup>V558A/WT</sup>/ZSWIM4<sup>-/-</sup> mice showed that loss of ZSWIM4 expression increases the expression of circadian clock pathway member BMAL1 which contributes to GIST cell survival and proliferation. In addition, we found that KIT signaling increases the distribution of ZSWIM4 in the nucleus of GIST cells, and which is important for its inhibition of KIT and BMAL1. In agreement with the results in vitro, the in vivo studies showed that ZSWIM4 deficiency increases the tumorigenesis of GISTs in KIT<sup>V558A/WT</sup> mice.</p><p><strong>Conclusions: </strong>Taken together, our results revealed that the entry of ZSWIM4 to the nucleus is important for its inhibition of KIT and BMAL1, ultimately attenuating GIST tumorigenesis. The results provide a novel insight in the understanding of signal transduction in GISTs and lay strong theoretical basis for the advancement of GIST treatment.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"87"},"PeriodicalIF":6.1000,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218225/pdf/","citationCount":"0","resultStr":"{\"title\":\"Entry of ZSWIM4 to the nucleus is crucial for its inhibition of KIT and BMAL1 in gastrointestinal stromal tumors.\",\"authors\":\"Xu Cao, Jinhai Tian, Man Yee Cheung, Liangying Zhang, Zimei Liu, Zongying Jiang, Shaoting Zhang, Kun Xiao, Sien Zhao, Ming Wang, Feng Ding, Shujing Li, Lijun Ma, Hui Zhao, Jianmin Sun\",\"doi\":\"10.1186/s13578-024-01271-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Zinc finger SWIM-type containing 4 (ZSWIM4) is a zinc finger protein with its function largely uncharacterized. In this study, we aimed to investigate the role of ZSWIM4 in gastrointestinal stromal tumors (GISTs).</p><p><strong>Results: </strong>We found that ZSWIM4 expression is inhibited by the predominantly mutated protein KIT in GISTs, while conversely, ZSWIM4 inhibits KIT expression and downstream signaling. Consistent with the observation, ZSWIM4 inhibited GIST cell survival and proliferation in vitro. RNA sequencing of GISTs from KIT<sup>V558A/WT</sup> mice and KIT<sup>V558A/WT</sup>/ZSWIM4<sup>-/-</sup> mice showed that loss of ZSWIM4 expression increases the expression of circadian clock pathway member BMAL1 which contributes to GIST cell survival and proliferation. In addition, we found that KIT signaling increases the distribution of ZSWIM4 in the nucleus of GIST cells, and which is important for its inhibition of KIT and BMAL1. In agreement with the results in vitro, the in vivo studies showed that ZSWIM4 deficiency increases the tumorigenesis of GISTs in KIT<sup>V558A/WT</sup> mice.</p><p><strong>Conclusions: </strong>Taken together, our results revealed that the entry of ZSWIM4 to the nucleus is important for its inhibition of KIT and BMAL1, ultimately attenuating GIST tumorigenesis. The results provide a novel insight in the understanding of signal transduction in GISTs and lay strong theoretical basis for the advancement of GIST treatment.</p>\",\"PeriodicalId\":49095,\"journal\":{\"name\":\"Cell and Bioscience\",\"volume\":\"14 1\",\"pages\":\"87\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-06-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218225/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell and Bioscience\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s13578-024-01271-z\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell and Bioscience","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13578-024-01271-z","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Entry of ZSWIM4 to the nucleus is crucial for its inhibition of KIT and BMAL1 in gastrointestinal stromal tumors.
Background: Zinc finger SWIM-type containing 4 (ZSWIM4) is a zinc finger protein with its function largely uncharacterized. In this study, we aimed to investigate the role of ZSWIM4 in gastrointestinal stromal tumors (GISTs).
Results: We found that ZSWIM4 expression is inhibited by the predominantly mutated protein KIT in GISTs, while conversely, ZSWIM4 inhibits KIT expression and downstream signaling. Consistent with the observation, ZSWIM4 inhibited GIST cell survival and proliferation in vitro. RNA sequencing of GISTs from KITV558A/WT mice and KITV558A/WT/ZSWIM4-/- mice showed that loss of ZSWIM4 expression increases the expression of circadian clock pathway member BMAL1 which contributes to GIST cell survival and proliferation. In addition, we found that KIT signaling increases the distribution of ZSWIM4 in the nucleus of GIST cells, and which is important for its inhibition of KIT and BMAL1. In agreement with the results in vitro, the in vivo studies showed that ZSWIM4 deficiency increases the tumorigenesis of GISTs in KITV558A/WT mice.
Conclusions: Taken together, our results revealed that the entry of ZSWIM4 to the nucleus is important for its inhibition of KIT and BMAL1, ultimately attenuating GIST tumorigenesis. The results provide a novel insight in the understanding of signal transduction in GISTs and lay strong theoretical basis for the advancement of GIST treatment.
期刊介绍：
Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.
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