Xiaoqing Shangguan, Xinping Zhang, Xiwu Chen, Zheng Zhang, Lei Wang
{"title":"神经上皮细胞转化1作为非小细胞肺癌的关键调节因子：揭示因果关系和治疗潜力","authors":"Xiaoqing Shangguan, Xinping Zhang, Xiwu Chen, Zheng Zhang, Lei Wang","doi":"10.21037/tcr-24-587","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>High incidence and mortality rates underscore lung cancer as a significant global health issue. Understanding the molecular mechanisms driving its progression is crucial for developing effective treatments. This study explores a potential molecular regulator that may contribute to the progression of non-small cell lung cancer (NSCLC) by utilizing bioinformatics analyses and laboratory experiments, aiming to provide insights that could inform future therapeutic strategies.</p><p><strong>Methods: </strong>Our research combined single-cell RNA sequencing (scRNA-seq) data analysis with the Mendelian randomization (MR) algorithm. MR analysis using genetic variants associated with NSCLC risk aimed to uncover causal relationships between genes and cancer traits. To validate the impact of neuroepithelial cell transforming 1 (<i>NET1</i>) on cellular proliferation and its role in inhibiting ferroptosis, we utilized quantitative real-time polymerase chain reaction (qRT-PCR), cell viability assays, and malondialdehyde (MDA) detection. Furthermore, molecular docking analyses of four compounds demonstrated their potential in modulating the downregulation of <i>NET1</i>.</p><p><strong>Results: </strong>ScRNA-seq exposed cellular diversity in non-malignant lungs and tumors. Distinct expression patterns in epithelial cells and identified gene pathways pointed to cell proliferation. <i>NET1</i>, causally linked to NSCLC through MR analysis, showed increased expression in tumors and correlated with unfavorable overall survival, validated by functional assays. Utilizing cell viability assays and MDA detection, our results validated the pivotal role of <i>NET1</i> in enhancing cellular proliferation and its efficacy in inhibiting ferroptosis. Doxorubicin, piroxicam, and quercetin emerged as potential drug candidates for NSCLC treatment based on molecular docking analysis.</p><p><strong>Conclusions: </strong>Our findings confirm <i>NET1</i>'s significant role in NSCLC progression, influencing cell proliferation, ferroptosis, immune activity regulation and identify potential therapeutics for targeted lung cancer treatment.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6087-6104"},"PeriodicalIF":1.5000,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651745/pdf/","citationCount":"0","resultStr":"{\"title\":\"Neuroepithelial cell transforming 1 as a key regulator in non-small cell lung cancer: unveiling causal links and therapeutic potentials.\",\"authors\":\"Xiaoqing Shangguan, Xinping Zhang, Xiwu Chen, Zheng Zhang, Lei Wang\",\"doi\":\"10.21037/tcr-24-587\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>High incidence and mortality rates underscore lung cancer as a significant global health issue. Understanding the molecular mechanisms driving its progression is crucial for developing effective treatments. This study explores a potential molecular regulator that may contribute to the progression of non-small cell lung cancer (NSCLC) by utilizing bioinformatics analyses and laboratory experiments, aiming to provide insights that could inform future therapeutic strategies.</p><p><strong>Methods: </strong>Our research combined single-cell RNA sequencing (scRNA-seq) data analysis with the Mendelian randomization (MR) algorithm. MR analysis using genetic variants associated with NSCLC risk aimed to uncover causal relationships between genes and cancer traits. To validate the impact of neuroepithelial cell transforming 1 (<i>NET1</i>) on cellular proliferation and its role in inhibiting ferroptosis, we utilized quantitative real-time polymerase chain reaction (qRT-PCR), cell viability assays, and malondialdehyde (MDA) detection. Furthermore, molecular docking analyses of four compounds demonstrated their potential in modulating the downregulation of <i>NET1</i>.</p><p><strong>Results: </strong>ScRNA-seq exposed cellular diversity in non-malignant lungs and tumors. Distinct expression patterns in epithelial cells and identified gene pathways pointed to cell proliferation. <i>NET1</i>, causally linked to NSCLC through MR analysis, showed increased expression in tumors and correlated with unfavorable overall survival, validated by functional assays. Utilizing cell viability assays and MDA detection, our results validated the pivotal role of <i>NET1</i> in enhancing cellular proliferation and its efficacy in inhibiting ferroptosis. Doxorubicin, piroxicam, and quercetin emerged as potential drug candidates for NSCLC treatment based on molecular docking analysis.</p><p><strong>Conclusions: </strong>Our findings confirm <i>NET1</i>'s significant role in NSCLC progression, influencing cell proliferation, ferroptosis, immune activity regulation and identify potential therapeutics for targeted lung cancer treatment.</p>\",\"PeriodicalId\":23216,\"journal\":{\"name\":\"Translational cancer research\",\"volume\":\"13 11\",\"pages\":\"6087-6104\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-11-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651745/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational cancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/tcr-24-587\",\"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}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-24-587","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}
Neuroepithelial cell transforming 1 as a key regulator in non-small cell lung cancer: unveiling causal links and therapeutic potentials.
Background: High incidence and mortality rates underscore lung cancer as a significant global health issue. Understanding the molecular mechanisms driving its progression is crucial for developing effective treatments. This study explores a potential molecular regulator that may contribute to the progression of non-small cell lung cancer (NSCLC) by utilizing bioinformatics analyses and laboratory experiments, aiming to provide insights that could inform future therapeutic strategies.
Methods: Our research combined single-cell RNA sequencing (scRNA-seq) data analysis with the Mendelian randomization (MR) algorithm. MR analysis using genetic variants associated with NSCLC risk aimed to uncover causal relationships between genes and cancer traits. To validate the impact of neuroepithelial cell transforming 1 (NET1) on cellular proliferation and its role in inhibiting ferroptosis, we utilized quantitative real-time polymerase chain reaction (qRT-PCR), cell viability assays, and malondialdehyde (MDA) detection. Furthermore, molecular docking analyses of four compounds demonstrated their potential in modulating the downregulation of NET1.
Results: ScRNA-seq exposed cellular diversity in non-malignant lungs and tumors. Distinct expression patterns in epithelial cells and identified gene pathways pointed to cell proliferation. NET1, causally linked to NSCLC through MR analysis, showed increased expression in tumors and correlated with unfavorable overall survival, validated by functional assays. Utilizing cell viability assays and MDA detection, our results validated the pivotal role of NET1 in enhancing cellular proliferation and its efficacy in inhibiting ferroptosis. Doxorubicin, piroxicam, and quercetin emerged as potential drug candidates for NSCLC treatment based on molecular docking analysis.
Conclusions: Our findings confirm NET1's significant role in NSCLC progression, influencing cell proliferation, ferroptosis, immune activity regulation and identify potential therapeutics for targeted lung cancer treatment.
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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