{"title":"DLX4 promotes the expression of PD-L1 through GATA1 in Gestational Trophoblastic Neoplasia.","authors":"Ying Wei, Chen Chen Zhu, Jiamu Xu, Weiping Hu, Jing Zhu","doi":"10.1016/j.tice.2024.102641","DOIUrl":null,"url":null,"abstract":"<p><p>Gestational Trophoblastic Neoplasia (GTN) is a highly malignant tumor that originates from trophoblastic cells during embryonic development. In this study, we observed that DLX4, a member of the Distal-Less Homeobox (Dlx) gene family, was upregulated in GTN tissues and cell lines. Bioinformatic analysis showed that DLX4 was highly expressed in most cancers and had a poor survival prognosis in certain tumors; further analysis showed that DLX4 was significantly associated with genes of immune pathways and immune infiltration. Functional analyses revealed that DLX4 overexpression or knockdown did not affect GTN cell proliferation; however, we observed that DLX4 could regulate PD-L1 expression via GATA1. The luciferase reporter activity of the wild-type construct increased after overexpression of GATA1, whereas the mutation of the binding sites abolished the transcriptional increase. In conclusion, our findings suggest that DLX4 regulates PD-L1 expression via GATA1 in GTN and may be a new target for antitumor therapy.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"102641"},"PeriodicalIF":2.7000,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue & cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.tice.2024.102641","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Gestational Trophoblastic Neoplasia (GTN) is a highly malignant tumor that originates from trophoblastic cells during embryonic development. In this study, we observed that DLX4, a member of the Distal-Less Homeobox (Dlx) gene family, was upregulated in GTN tissues and cell lines. Bioinformatic analysis showed that DLX4 was highly expressed in most cancers and had a poor survival prognosis in certain tumors; further analysis showed that DLX4 was significantly associated with genes of immune pathways and immune infiltration. Functional analyses revealed that DLX4 overexpression or knockdown did not affect GTN cell proliferation; however, we observed that DLX4 could regulate PD-L1 expression via GATA1. The luciferase reporter activity of the wild-type construct increased after overexpression of GATA1, whereas the mutation of the binding sites abolished the transcriptional increase. In conclusion, our findings suggest that DLX4 regulates PD-L1 expression via GATA1 in GTN and may be a new target for antitumor therapy.
期刊介绍：
Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed.
Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.
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