{"title":"LncRNA ZEB1-AS1 promotes the proliferation and migration of non-small cell lung cancer by activating epithelial-mesenchymal transition with STAT3.","authors":"Zhengjin Chen, Yangwei Yao, Jingpeng Gao","doi":"10.21037/tcr-2024-2276","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the most common cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) is the main type of lung cancer. Long non-coding RNA ZEB1 antisense 1 (lncRNA ZEB1-AS1) is derived from the promoter region of the transcriptional repressor ZEB1. In bladder cancer and glioblastoma, lncRNA ZEB1-AS1 promotes the expression of ZEB1 and cancer progression, and is associated with a poor prognosis. However, its role in NSCLC tumor progression remains unclear. This study aims to investigate its possible role in NSCLC tumor progression.</p><p><strong>Methods: </strong>In this study, overexpressed and silenced lncRNA NSCLC cell lines of ZEB1-AS1 were constructed, epithelial-mesenchymal transition (EMT)-related proteins were detected, and the invasion and migration abilities of the cells were examined. Moreover, the radioimmunoprecipitation (RIP) assay was used to examine whether the increase in the STAT3 protein level caused by ZEB1-AS1 overexpression was based on the promotion of STAT3 messenger RNA (mRNA) translation by AUF1, and the dual-luciferase assay was used to verify the results.</p><p><strong>Results: </strong>The overexpression of ZEB1-AS1 increased the protein levels of ZEB1 and STAT3, promoted the occurrence of EMT, and enhanced the invasion and migration abilities of lung cancer cells. The RIP results showed that both lncRNA ZEB1-AS1 and <i>ZEB1</i> mRNA bind to AUF1, but no binding between AUF1 and <i>STAT3</i> mRNA was detected. The bioinformatics analysis and the results of the dual-luciferase experiments showed that <i>STAT3</i> was the target gene of microRNA 519d (miRNA519d), and that lncRNA ZEB1-AS1 also binds to miRNA519d.</p><p><strong>Conclusions: </strong>LncRNA ZEB1-AS1 formed the competing endogenous RNA (ceRNA) regulatory network of lncRNA ZEB1-AS1~miRNA519d~STAT3 as the molecular sponge, and promoted the expression of STAT3, thus promoting the occurrence of EMT in lung cancer cells.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 1","pages":"584-594"},"PeriodicalIF":1.5000,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833408/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-2024-2276","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/23 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Lung cancer is the most common cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) is the main type of lung cancer. Long non-coding RNA ZEB1 antisense 1 (lncRNA ZEB1-AS1) is derived from the promoter region of the transcriptional repressor ZEB1. In bladder cancer and glioblastoma, lncRNA ZEB1-AS1 promotes the expression of ZEB1 and cancer progression, and is associated with a poor prognosis. However, its role in NSCLC tumor progression remains unclear. This study aims to investigate its possible role in NSCLC tumor progression.
Methods: In this study, overexpressed and silenced lncRNA NSCLC cell lines of ZEB1-AS1 were constructed, epithelial-mesenchymal transition (EMT)-related proteins were detected, and the invasion and migration abilities of the cells were examined. Moreover, the radioimmunoprecipitation (RIP) assay was used to examine whether the increase in the STAT3 protein level caused by ZEB1-AS1 overexpression was based on the promotion of STAT3 messenger RNA (mRNA) translation by AUF1, and the dual-luciferase assay was used to verify the results.
Results: The overexpression of ZEB1-AS1 increased the protein levels of ZEB1 and STAT3, promoted the occurrence of EMT, and enhanced the invasion and migration abilities of lung cancer cells. The RIP results showed that both lncRNA ZEB1-AS1 and ZEB1 mRNA bind to AUF1, but no binding between AUF1 and STAT3 mRNA was detected. The bioinformatics analysis and the results of the dual-luciferase experiments showed that STAT3 was the target gene of microRNA 519d (miRNA519d), and that lncRNA ZEB1-AS1 also binds to miRNA519d.
Conclusions: LncRNA ZEB1-AS1 formed the competing endogenous RNA (ceRNA) regulatory network of lncRNA ZEB1-AS1~miRNA519d~STAT3 as the molecular sponge, and promoted the expression of STAT3, thus promoting the occurrence of EMT in lung cancer cells.
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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