{"title":"Transcription Factor yin-Yang 1 augments nucleoporin 93 oncogene activity and modulates bladder Cancer malignancy","authors":"Gang Zhang , Wei Wei , Shao Li , Jinyi Yang","doi":"10.1016/j.tiv.2024.105875","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>This study aims to investigate the functional interplay between transcription factor YY1 and nucleoporin 93 (NUP93) in regulating the malignancy of bladder cancer cells.</p></div><div><h3>Methods</h3><p>NUP93 expressions in bladder cancer tissues and normal counterparts were analyzed using a public dataset and clinical samples. NUP93 and Yin Yang 1 (YY1) mRNA expression and protein levels in T24 and RT4 cells were determined by Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The effect of NUP93 knockdown on the proliferation, migration, and invasion capabilities of cells was evaluated. Concurrently, transcriptional regulation of NUP93 by YY1 was confirmed using a dual luciferase assay. The effect of NUP93 knockdown on tumorigenesis was evaluate in a subcutaneous xenograft mouse model.</p></div><div><h3>Results</h3><p>Elevated levels of NUP93 in bladder cancer tissues and cell lines were observed. Silencing NUP93 significantly suppressed glycolysis, impeded the growth, migration, invasion and tumor formation of bladder cancer cells. The transcription factor YY1 acted as a positive regulator to upregulate NUP93 expression. YY1 overexpression partially rescued the effects of NUP93 silencing on bladder cancer cells.</p></div><div><h3>Conclusion</h3><p>Our results uncovered transcription factor YY1 as a positive regulator of NUP93 expression, and NUP93 serves as an oncogenic factor to sustain the malignancy of bladder cancer cells. These findings suggest that targeting the YY1-NUP93 axis could offer novel therapeutic strategies for bladder cancer treatment.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105875"},"PeriodicalIF":2.6000,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology in Vitro","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S088723332400105X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective
This study aims to investigate the functional interplay between transcription factor YY1 and nucleoporin 93 (NUP93) in regulating the malignancy of bladder cancer cells.
Methods
NUP93 expressions in bladder cancer tissues and normal counterparts were analyzed using a public dataset and clinical samples. NUP93 and Yin Yang 1 (YY1) mRNA expression and protein levels in T24 and RT4 cells were determined by Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The effect of NUP93 knockdown on the proliferation, migration, and invasion capabilities of cells was evaluated. Concurrently, transcriptional regulation of NUP93 by YY1 was confirmed using a dual luciferase assay. The effect of NUP93 knockdown on tumorigenesis was evaluate in a subcutaneous xenograft mouse model.
Results
Elevated levels of NUP93 in bladder cancer tissues and cell lines were observed. Silencing NUP93 significantly suppressed glycolysis, impeded the growth, migration, invasion and tumor formation of bladder cancer cells. The transcription factor YY1 acted as a positive regulator to upregulate NUP93 expression. YY1 overexpression partially rescued the effects of NUP93 silencing on bladder cancer cells.
Conclusion
Our results uncovered transcription factor YY1 as a positive regulator of NUP93 expression, and NUP93 serves as an oncogenic factor to sustain the malignancy of bladder cancer cells. These findings suggest that targeting the YY1-NUP93 axis could offer novel therapeutic strategies for bladder cancer treatment.
期刊介绍：
Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.
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