Jiangang Xu, Liyin Zhang, Menghui Feng, Weijun Hong, Xinming Ye
{"title":"Postexercise downregulation of <i>NUP155</i> in regulating non-small cell lung cancer progression via the PTEN/AKT signaling pathway.","authors":"Jiangang Xu, Liyin Zhang, Menghui Feng, Weijun Hong, Xinming Ye","doi":"10.21037/tcr-24-1619","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Research interest into regulation of gene expression by physical activity and its effect on cancer prognosis has intensified. This study investigated the role of an exercise-related gene, <i>NUP155</i>, in the progression of non-small cell lung cancer (NSCLC) and its potential as therapy target.</p><p><strong>Methods: </strong>Using the GSE41914 dataset, which includes data related to exercise, and the Cancer Genome Atlas (TCGA)-NSCLC dataset, we identified differentially expressed genes (DEGs) and selected <i>NUP155</i> as a hub gene for further analysis. <i>NUP155</i> expression levels were measured in NSCLC cell lines and normal lung cells using <i>in vitro</i> assays. The functional roles of <i>NUP155</i> were investigated through small interfering RNA (siRNA) knockdown experiments, assessing effects on migration, cell proliferation, invasion, and apoptosis. The involvement of the PTEN/AKT signaling pathway was examined using the PTEN inhibitor SF1670.</p><p><strong>Results: </strong><i>NUP155</i> was downregulated in postexercise samples and upregulated in NSCLC samples, indicating its association with poor prognosis in NSCLC. Knockdown of <i>NUP155</i> in NSCLC cell lines resulted in reduced cell viability, migration, and invasion, alongside increased apoptosis. Western blotting revealed that <i>NUP155</i> knockdown upregulated PTEN levels and downregulated phosphorylated AKT (p-AKT), without altering total AKT levels. The addition of SF1670 partially reversed the effects of <i>NUP155</i> knockdown, indicating the involvement of the signaling pathway PTEN/AKT in <i>NUP155</i>-mediated tumorigenesis.</p><p><strong>Conclusions: </strong><i>NUP155</i> is upregulated in NSCLC, which promotes cell invasion and migration via the PTEN/AKT signaling pathway. Targeting <i>NUP155</i>, potentially influenced by exercise, could be a promising therapy. Combining exercise with targeted treatments may enhance patient outcomes.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6323-6335"},"PeriodicalIF":1.5000,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651763/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-24-1619","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/27 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Research interest into regulation of gene expression by physical activity and its effect on cancer prognosis has intensified. This study investigated the role of an exercise-related gene, NUP155, in the progression of non-small cell lung cancer (NSCLC) and its potential as therapy target.
Methods: Using the GSE41914 dataset, which includes data related to exercise, and the Cancer Genome Atlas (TCGA)-NSCLC dataset, we identified differentially expressed genes (DEGs) and selected NUP155 as a hub gene for further analysis. NUP155 expression levels were measured in NSCLC cell lines and normal lung cells using in vitro assays. The functional roles of NUP155 were investigated through small interfering RNA (siRNA) knockdown experiments, assessing effects on migration, cell proliferation, invasion, and apoptosis. The involvement of the PTEN/AKT signaling pathway was examined using the PTEN inhibitor SF1670.
Results: NUP155 was downregulated in postexercise samples and upregulated in NSCLC samples, indicating its association with poor prognosis in NSCLC. Knockdown of NUP155 in NSCLC cell lines resulted in reduced cell viability, migration, and invasion, alongside increased apoptosis. Western blotting revealed that NUP155 knockdown upregulated PTEN levels and downregulated phosphorylated AKT (p-AKT), without altering total AKT levels. The addition of SF1670 partially reversed the effects of NUP155 knockdown, indicating the involvement of the signaling pathway PTEN/AKT in NUP155-mediated tumorigenesis.
Conclusions: NUP155 is upregulated in NSCLC, which promotes cell invasion and migration via the PTEN/AKT signaling pathway. Targeting NUP155, potentially influenced by exercise, could be a promising therapy. Combining exercise with targeted treatments may enhance patient outcomes.
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.