Postexercise downregulation of NUP155 in regulating non-small cell lung cancer progression via the PTEN/AKT signaling pathway.

IF 1.5 4区 医学 Q4 ONCOLOGY
Translational cancer research Pub Date : 2024-11-30 Epub Date: 2024-11-27 DOI:10.21037/tcr-24-1619
Jiangang Xu, Liyin Zhang, Menghui Feng, Weijun Hong, Xinming Ye
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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.

运动后下调NUP155通过PTEN/AKT信号通路调节非小细胞肺癌的进展。
背景:体育锻炼对基因表达的调控及其对肿瘤预后的影响已成为研究热点。本研究探讨了运动相关基因NUP155在非小细胞肺癌(NSCLC)进展中的作用及其作为治疗靶点的潜力。方法:利用GSE41914数据集(包括与运动相关的数据)和癌症基因组图谱(TCGA)-NSCLC数据集,我们确定了差异表达基因(DEGs),并选择NUP155作为中心基因进行进一步分析。NUP155在非小细胞肺癌细胞系和正常肺细胞中的表达水平通过体外测定。通过小干扰RNA (siRNA)敲低实验研究NUP155的功能作用,评估其对迁移、细胞增殖、侵袭和凋亡的影响。使用PTEN抑制剂SF1670检测PTEN/AKT信号通路的参与情况。结果:NUP155在运动后样本中表达下调,在NSCLC样本中表达上调,提示其与NSCLC预后不良相关。在NSCLC细胞系中,NUP155的敲低导致细胞活力、迁移和侵袭降低,同时细胞凋亡增加。Western blotting结果显示,NUP155敲低可上调PTEN水平,下调磷酸化AKT (p-AKT)水平,但不改变总AKT水平。SF1670的加入部分逆转了NUP155敲低的作用,表明PTEN/AKT信号通路参与了NUP155介导的肿瘤发生。结论:NUP155在NSCLC中表达上调,通过PTEN/AKT信号通路促进细胞侵袭和迁移。针对可能受运动影响的NUP155,可能是一种有希望的治疗方法。将运动与有针对性的治疗相结合可能会提高患者的预后。
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来源期刊
CiteScore
2.10
自引率
0.00%
发文量
252
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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