HAMP 预测在调节非小细胞肺癌细胞的恶性行为中发挥关键作用。
HAMP predicts a pivotal role in modulating the malignant behaviors of non-small cell lung cancer cells.
机构信息
Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Department of Respiratory Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China.
出版信息
Aging (Albany NY). 2024 May 22;16(10):8524-8540. doi: 10.18632/aging.205819.
BACKGROUND
Hepcidin antimicrobial peptide (HAMP) is a small peptide hormone recognized for its role in iron metabolism and cancer treatment. The purpose of this study was to examine the influence of HAMP in NSCLC.
METHODS
The profile of NSCLC cells and tissues was characterized via HAMP. Gain- or loss-of-function cell models of HAMP were constructed, and CCK8, colony formation, and Transwell analyses were used to confirm the influence of HAMP on NSCLC cells. Upstream and downstream HAMP mechanisms in NSCLC were also analysed. Dual-luciferase reporter and pull-down assays confirmed the associations of miR-873-5p with HAMP, miR-873-5p, and the lncRNA KCNQ1OT1/SNHG14/XIST. Moreover, a xenograft model was established in nude mice for confirming the role of HAMP in NSCLC cell growth.
RESULTS
In addition, HAMP expression increased in NSCLC cells and tissues. In terms of cellular functions, the HAMP-overexpressing group exhibited elevated NSCLC cell proliferation, invasion, and migration. HAMP knockdown reversed these changes. Bioinformatics analysis indicated that miR-873-5p targeted HAMP, which affected the nuclear factor kappa B (NF-κB) pathway in NSCLC. HAMP activated the NF-κB pathway, which was negatively modulated by miR-873-5p. NF-κB inhibitor JSH-23 can partly suppress the proliferation, invasion, and migration in HAMP-overexpressed cells. Moreover, miR-873-5p was the target miRNA of long noncoding RNAs (lncRNAs), which included KCNQ1OT1, SNHG14, and XIST, and these three lncRNAs promoted HAMP.
CONCLUSION
Noncoding RNA-mediated HAMP promotes NSCLC cell proliferation, migration, and invasion by initiating the NF-κB pathway.
背景
抗菌肽（HAMP）是一种小肽激素，因其在铁代谢和癌症治疗中的作用而被广泛认可。本研究旨在研究 HAMP 在非小细胞肺癌（NSCLC）中的作用。
方法
通过 HAMP 对 NSCLC 细胞和组织的特征进行了描述。构建了 HAMP 的增益或失能细胞模型，并使用 CCK8、集落形成和 Transwell 分析来验证 HAMP 对 NSCLC 细胞的影响。还分析了 NSCLC 中 HAMP 的上下游机制。双荧光素酶报告和下拉实验证实了 miR-873-5p 与 HAMP、miR-873-5p 和 lncRNA KCNQ1OT1/SNHG14/XIST 的关联。此外，还在裸鼠中建立了异种移植模型，以验证 HAMP 在 NSCLC 细胞生长中的作用。
结果
此外，HAMP 在 NSCLC 细胞和组织中的表达增加。在细胞功能方面，HAMP 过表达组表现出 NSCLC 细胞增殖、侵袭和迁移的增强。HAMP 敲低逆转了这些变化。生物信息学分析表明，miR-873-5p 靶向 HAMP，影响 NSCLC 中的核因子 kappa B（NF-κB）途径。HAMP 激活了 NF-κB 途径，而 miR-873-5p 对其进行了负调节。NF-κB 抑制剂 JSH-23 可部分抑制 HAMP 过表达细胞的增殖、侵袭和迁移。此外，miR-873-5p 是长链非编码 RNA（lncRNA）的靶 miRNA，包括 KCNQ1OT1、SNHG14 和 XIST，这三个 lncRNA 促进了 HAMP。
结论
非编码 RNA 介导的 HAMP 通过启动 NF-κB 途径促进 NSCLC 细胞的增殖、迁移和侵袭。
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