Yafu Zhou, Huiguo Chen, Jianhua Yan, Qi Yao, Chunchu Kong, You Peng, Shengying Xiao, Jinsong Yang
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Meanwhile, we performed abnormal expression treatment on RND1 and conducted CCK8, colony formation, and flow cytometry to evaluate the impact of RND1 expression on cell proliferation, apoptosis, and DDP resistance. In addition, we analyzed metabolism pathways involving RND1 using GSEA. We also used online tools such as hTFtarget and JASPAR to screen for the upstream transcription factor FOXA2 of RND1 and verified their relationship through CHIP and dual luciferase experiments. Finally, we validated the role of FOXA2-RND1 in DDP resistance in LUSC through the above experiments.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>RND1 was downregulated in LUSC, and overexpression of RND1 repressed proliferation and DDP resistance of LUSC cells and facilitated cell apoptosis. RND1 modulated the arachidonic acid (AA) metabolism pathway, and FOXA2 positively manipulated RND1 expression. By activating FOXA2, stabilizing RND1, and regulating AA levels, the sensitivity of LUSC cells to DDP could be enhanced.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our study suggested that FOXA2 positively modulated the RND1-AA pathway, which repressed the resistance of LUSC cells to DDP.</p>\n </section>\n </div>","PeriodicalId":55247,"journal":{"name":"Clinical Respiratory Journal","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/crj.13814","citationCount":"0","resultStr":"{\"title\":\"FOXA2 Activates RND1 to Regulate Arachidonic Acid Metabolism Pathway and Suppress Cisplatin Resistance in Lung Squamous Cell Carcinoma\",\"authors\":\"Yafu Zhou, Huiguo Chen, Jianhua Yan, Qi Yao, Chunchu Kong, You Peng, Shengying Xiao, Jinsong Yang\",\"doi\":\"10.1111/crj.13814\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>The primary cause of cancer-related fatalities globally is lung cancer. Although the chemotherapy drug cisplatin (DDP) has brought certain benefits to patients, the rapid development of drug resistance has greatly hindered treatment success.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We used the lung squamous cell carcinoma (LUSC) mRNA data set to explore the differentially expressed gene (RND1) in LUSC and detected RND1 expression in LUSC cells and DDP-resistant cells by qRT-PCR. Meanwhile, we performed abnormal expression treatment on RND1 and conducted CCK8, colony formation, and flow cytometry to evaluate the impact of RND1 expression on cell proliferation, apoptosis, and DDP resistance. In addition, we analyzed metabolism pathways involving RND1 using GSEA. We also used online tools such as hTFtarget and JASPAR to screen for the upstream transcription factor FOXA2 of RND1 and verified their relationship through CHIP and dual luciferase experiments. 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FOXA2 Activates RND1 to Regulate Arachidonic Acid Metabolism Pathway and Suppress Cisplatin Resistance in Lung Squamous Cell Carcinoma
Background
The primary cause of cancer-related fatalities globally is lung cancer. Although the chemotherapy drug cisplatin (DDP) has brought certain benefits to patients, the rapid development of drug resistance has greatly hindered treatment success.
Methods
We used the lung squamous cell carcinoma (LUSC) mRNA data set to explore the differentially expressed gene (RND1) in LUSC and detected RND1 expression in LUSC cells and DDP-resistant cells by qRT-PCR. Meanwhile, we performed abnormal expression treatment on RND1 and conducted CCK8, colony formation, and flow cytometry to evaluate the impact of RND1 expression on cell proliferation, apoptosis, and DDP resistance. In addition, we analyzed metabolism pathways involving RND1 using GSEA. We also used online tools such as hTFtarget and JASPAR to screen for the upstream transcription factor FOXA2 of RND1 and verified their relationship through CHIP and dual luciferase experiments. Finally, we validated the role of FOXA2-RND1 in DDP resistance in LUSC through the above experiments.
Results
RND1 was downregulated in LUSC, and overexpression of RND1 repressed proliferation and DDP resistance of LUSC cells and facilitated cell apoptosis. RND1 modulated the arachidonic acid (AA) metabolism pathway, and FOXA2 positively manipulated RND1 expression. By activating FOXA2, stabilizing RND1, and regulating AA levels, the sensitivity of LUSC cells to DDP could be enhanced.
Conclusion
Our study suggested that FOXA2 positively modulated the RND1-AA pathway, which repressed the resistance of LUSC cells to DDP.
期刊介绍:
Overview
Effective with the 2016 volume, this journal will be published in an online-only format.
Aims and Scope
The Clinical Respiratory Journal (CRJ) provides a forum for clinical research in all areas of respiratory medicine from clinical lung disease to basic research relevant to the clinic.
We publish original research, review articles, case studies, editorials and book reviews in all areas of clinical lung disease including:
Asthma
Allergy
COPD
Non-invasive ventilation
Sleep related breathing disorders
Interstitial lung diseases
Lung cancer
Clinical genetics
Rhinitis
Airway and lung infection
Epidemiology
Pediatrics
CRJ provides a fast-track service for selected Phase II and Phase III trial studies.
Keywords
Clinical Respiratory Journal, respiratory, pulmonary, medicine, clinical, lung disease,
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