Xiaoming Fang, Xinyu Zhang, Ping Liu, Dan Yu, Andrzej Swierniak, Carl G Maki, Ruichen Gao, Ming Liu
{"title":"ISG20L2通过NKX2-1调控在肺腺癌增殖和侵袭中的驱动作用","authors":"Xiaoming Fang, Xinyu Zhang, Ping Liu, Dan Yu, Andrzej Swierniak, Carl G Maki, Ruichen Gao, Ming Liu","doi":"10.21037/tcr-2025-1546","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Interferon-stimulated 20-kDa exonuclease-like 2 (<i>ISG20L2</i>) is a gene that shows variable expression levels in lung adenocarcinoma (LUAD). Despite this, its role and expression in LUAD have not been well characterized. This study focused on analyzing the expression of <i>ISG20L2</i> in LUAD, its association with patient prognosis, and its potential regulatory influence on NK2 homeobox 1 (<i>NKX2-1</i>) in LUAD cells.</p><p><strong>Methods: </strong>We used The Cancer Genome Atlas (TCGA) database and immunohistochemistry to assess the expression of <i>ISG20L2</i>. Kaplan-Meier survival analysis was employed to determine the relationship between <i>ISG20L2</i> expression and prognosis in patients with LUAD. The diagnostic potential of <i>ISG20L2</i> in LUAD was evaluated through receiving operating characteristic curve analysis. The association between <i>ISG20L2</i> expression and clinicopathological features was analyzed with the Fisher exact test. Overexpression and depletion studies of <i>ISG20L2</i> were performed via transient transfection. The biological functions of <i>ISG20L2</i> in A549 cells, such as cell proliferation, apoptosis, migration, and invasion, were examined via Cell Counting Kit-8 (CCK-8), flow cytometry, and Transwell assays. Bioinformatics analysis suggested a link between <i>ISG20L2</i> and <i>NKX2-1</i>, which was subsequently confirmed through cytological experiments.</p><p><strong>Results: </strong>Our results demonstrated that <i>ISG20L2</i> was overexpressed in LUAD, and this overexpression was significantly correlated with poor prognosis. <i>In vitro</i> experiments further supported a positive association between <i>ISG20L2</i> expression and the proliferative, migratory, and invasive capabilities in A549 cells, with no notable effect on apoptosis. Functional assays confirmed that <i>ISG20L2</i> enhanced A549 cell proliferation and invasion by modulating <i>NKX2-1</i>.</p><p><strong>Conclusions: </strong><i>ISG20L2</i> promotes LUAD progression via <i>NKX2-1</i> regulation, implying the potential of the <i>ISG20L2/NKX2-1</i> axis as a candidate biomarker and therapeutic target in LUAD.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"5028-5044"},"PeriodicalIF":1.7000,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432785/pdf/","citationCount":"0","resultStr":"{\"title\":\"<i>ISG20L2</i> as a driver in the proliferation and invasion of lung adenocarcinoma via <i>NKX2-1</i> regulation.\",\"authors\":\"Xiaoming Fang, Xinyu Zhang, Ping Liu, Dan Yu, Andrzej Swierniak, Carl G Maki, Ruichen Gao, Ming Liu\",\"doi\":\"10.21037/tcr-2025-1546\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Interferon-stimulated 20-kDa exonuclease-like 2 (<i>ISG20L2</i>) is a gene that shows variable expression levels in lung adenocarcinoma (LUAD). Despite this, its role and expression in LUAD have not been well characterized. This study focused on analyzing the expression of <i>ISG20L2</i> in LUAD, its association with patient prognosis, and its potential regulatory influence on NK2 homeobox 1 (<i>NKX2-1</i>) in LUAD cells.</p><p><strong>Methods: </strong>We used The Cancer Genome Atlas (TCGA) database and immunohistochemistry to assess the expression of <i>ISG20L2</i>. Kaplan-Meier survival analysis was employed to determine the relationship between <i>ISG20L2</i> expression and prognosis in patients with LUAD. The diagnostic potential of <i>ISG20L2</i> in LUAD was evaluated through receiving operating characteristic curve analysis. The association between <i>ISG20L2</i> expression and clinicopathological features was analyzed with the Fisher exact test. Overexpression and depletion studies of <i>ISG20L2</i> were performed via transient transfection. The biological functions of <i>ISG20L2</i> in A549 cells, such as cell proliferation, apoptosis, migration, and invasion, were examined via Cell Counting Kit-8 (CCK-8), flow cytometry, and Transwell assays. Bioinformatics analysis suggested a link between <i>ISG20L2</i> and <i>NKX2-1</i>, which was subsequently confirmed through cytological experiments.</p><p><strong>Results: </strong>Our results demonstrated that <i>ISG20L2</i> was overexpressed in LUAD, and this overexpression was significantly correlated with poor prognosis. <i>In vitro</i> experiments further supported a positive association between <i>ISG20L2</i> expression and the proliferative, migratory, and invasive capabilities in A549 cells, with no notable effect on apoptosis. Functional assays confirmed that <i>ISG20L2</i> enhanced A549 cell proliferation and invasion by modulating <i>NKX2-1</i>.</p><p><strong>Conclusions: </strong><i>ISG20L2</i> promotes LUAD progression via <i>NKX2-1</i> regulation, implying the potential of the <i>ISG20L2/NKX2-1</i> axis as a candidate biomarker and therapeutic target in LUAD.</p>\",\"PeriodicalId\":23216,\"journal\":{\"name\":\"Translational cancer research\",\"volume\":\"14 8\",\"pages\":\"5028-5044\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-08-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432785/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational cancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/tcr-2025-1546\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-2025-1546","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/27 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
ISG20L2 as a driver in the proliferation and invasion of lung adenocarcinoma via NKX2-1 regulation.
Background: Interferon-stimulated 20-kDa exonuclease-like 2 (ISG20L2) is a gene that shows variable expression levels in lung adenocarcinoma (LUAD). Despite this, its role and expression in LUAD have not been well characterized. This study focused on analyzing the expression of ISG20L2 in LUAD, its association with patient prognosis, and its potential regulatory influence on NK2 homeobox 1 (NKX2-1) in LUAD cells.
Methods: We used The Cancer Genome Atlas (TCGA) database and immunohistochemistry to assess the expression of ISG20L2. Kaplan-Meier survival analysis was employed to determine the relationship between ISG20L2 expression and prognosis in patients with LUAD. The diagnostic potential of ISG20L2 in LUAD was evaluated through receiving operating characteristic curve analysis. The association between ISG20L2 expression and clinicopathological features was analyzed with the Fisher exact test. Overexpression and depletion studies of ISG20L2 were performed via transient transfection. The biological functions of ISG20L2 in A549 cells, such as cell proliferation, apoptosis, migration, and invasion, were examined via Cell Counting Kit-8 (CCK-8), flow cytometry, and Transwell assays. Bioinformatics analysis suggested a link between ISG20L2 and NKX2-1, which was subsequently confirmed through cytological experiments.
Results: Our results demonstrated that ISG20L2 was overexpressed in LUAD, and this overexpression was significantly correlated with poor prognosis. In vitro experiments further supported a positive association between ISG20L2 expression and the proliferative, migratory, and invasive capabilities in A549 cells, with no notable effect on apoptosis. Functional assays confirmed that ISG20L2 enhanced A549 cell proliferation and invasion by modulating NKX2-1.
Conclusions: ISG20L2 promotes LUAD progression via NKX2-1 regulation, implying the potential of the ISG20L2/NKX2-1 axis as a candidate biomarker and therapeutic target in LUAD.
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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