FOXA2 Activates RND1 to Regulate Arachidonic Acid Metabolism Pathway and Suppress Cisplatin Resistance in Lung Squamous Cell Carcinoma

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal Pub Date : 2024-08-11 DOI:10.1111/crj.13814

Yafu Zhou, Huiguo Chen, Jianhua Yan, Qi Yao, Chunchu Kong, You Peng, Shengying Xiao, Jinsong Yang

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引用次数: 0

Abstract

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.

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FOXA2 激活 RND1 以调节花生四烯酸代谢途径并抑制肺鳞癌的顺铂抗性

背景：肺癌是全球癌症致死的主要原因。尽管化疗药物顺铂（DDP）给患者带来了一定的益处，但耐药性的迅速发展极大地阻碍了治疗的成功：方法：我们利用肺鳞状细胞癌（LUSC）mRNA数据集探索肺鳞状细胞癌中的差异表达基因（RND1），并通过qRT-PCR检测RND1在肺鳞状细胞癌细胞和DDP耐药细胞中的表达。同时，我们对 RND1 进行了异常表达处理，并通过 CCK8、集落形成和流式细胞术评估了 RND1 表达对细胞增殖、凋亡和 DDP 抗性的影响。此外，我们还利用 GSEA 分析了涉及 RND1 的代谢通路。我们还利用 hTFtarget 和 JASPAR 等在线工具筛选了 RND1 的上游转录因子 FOXA2，并通过 CHIP 和双荧光素酶实验验证了它们之间的关系。最后，我们通过上述实验验证了 FOXA2-RND1 在 LUSC DDP 抗性中的作用：结果：RND1在LUSC中下调，过表达RND1抑制了LUSC细胞的增殖和DDP抗性，并促进了细胞凋亡。RND1调节花生四烯酸（AA）代谢途径，而FOXA2对RND1的表达有积极的调节作用。通过激活 FOXA2、稳定 RND1 和调节 AA 水平，可提高 LUSC 细胞对 DDP 的敏感性：我们的研究表明，FOXA2能积极调节RND1-AA通路，从而抑制LUSC细胞对DDP的抗性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Respiratory Journal 医学-呼吸系统

CiteScore

3.70

自引率

0.00%

发文量

104

审稿时长

>12 weeks

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, Abstracting and Indexing Information Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Embase (Elsevier) Health & Medical Collection (ProQuest) Health Research Premium Collection (ProQuest) HEED: Health Economic Evaluations Database (Wiley-Blackwell) Hospital Premium Collection (ProQuest) Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) ProQuest Central (ProQuest) Science Citation Index Expanded (Clarivate Analytics) SCOPUS (Elsevier)

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