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铜死亡相关 ceRNA 轴通过 CBX2 触发肺腺癌中的细胞增殖和细胞周期。

Cuproptosis-related ceRNA axis triggers cell proliferation and cell cycle through CBX2 in lung adenocarcinoma.

机构信息

Department of Thoracic Surgery, Xinqiao Hospital, Army Medical University, 400037, Chongqing, China.

出版信息

BMC Pulm Med. 2024 Feb 14;24(1):85. doi: 10.1186/s12890-024-02887-0.

Abstract

BACKGROUND

Lung adenocarcinoma (LUAD) has high morbidity and mortality. Despite substantial advances in treatment, the prognosis of patients with LUAD remains unfavorable. The ceRNA axis has been reported to play an important role in the pathogenesis of LUAD. In addition, cuproptosis is considered an important factor in tumorigenesis. The expression of CBX2 has been associated with the development of multiple tumors, including LUAD. However, the precise molecular mechanisms through which the cuproptosis-related ceRNA network regulates CBX2 remain unclear.

METHODS

The DEGs between tumor and normal samples of LUAD were identified in TCGA database. The "ConsensusClusterPlus" R package was used to perform consensus clustering based on the mRNA expression matrix and cuproptosis-related gene expression profile. Then, LASSO-COX regression analysis was performed to identify potential prognostic biomarkers associated with cuproptosis, and the ceRNA network was constructed. Finally, the mechanisms of ceRNA in LUAD was studied by cell experiments.

RESULTS

In this study, the AC144450.1/miR-424-5p axis was found to promote the progression of LUAD by acting on CBX2. The expression of AC144450.1 and miR-424-5p can be altered to regulate CBX2 and is correlated with cell proliferation and cell cycle of LUAD. Mechanistically, AC144450.1 affects the expression of CBX2 by acting as the ceRNA of miR-424-5p. In addition, a cuproptosis-related model were constructed in this study to predict the prognosis of LUAD.

CONCLUSIONS

This study is the first to demonstrate that the AC144450.1/miR-424-5p/CBX2 axis is involved in LUAD progression and may serve as a novel target for its diagnosis and treatment.

摘要

背景

肺腺癌 (LUAD) 具有高发病率和死亡率。尽管在治疗方面取得了重大进展,但 LUAD 患者的预后仍然不佳。ceRNA 轴已被报道在 LUAD 的发病机制中发挥重要作用。此外,铜死亡被认为是肿瘤发生的一个重要因素。CBX2 的表达与多种肿瘤的发生有关,包括 LUAD。然而,铜死亡相关 ceRNA 网络调节 CBX2 的精确分子机制尚不清楚。

方法

在 TCGA 数据库中鉴定 LUAD 肿瘤组织和正常组织之间的差异表达基因。使用“ConsensusClusterPlus”R 包根据 mRNA 表达矩阵和铜死亡相关基因表达谱进行共识聚类。然后,进行 LASSO-COX 回归分析,以确定与铜死亡相关的潜在预后生物标志物,并构建 ceRNA 网络。最后,通过细胞实验研究 ceRNA 在 LUAD 中的作用机制。

结果

在这项研究中,发现 AC144450.1/miR-424-5p 轴通过作用于 CBX2 促进 LUAD 的进展。AC144450.1 和 miR-424-5p 的表达可以改变来调节 CBX2,并且与 LUAD 的细胞增殖和细胞周期相关。机制上,AC144450.1 通过作为 miR-424-5p 的 ceRNA 来影响 CBX2 的表达。此外,本研究构建了一个铜死亡相关模型来预测 LUAD 的预后。

结论

这项研究首次表明,AC144450.1/miR-424-5p/CBX2 轴参与 LUAD 的进展,可能成为其诊断和治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/166e/10865584/b5aef3811e4e/12890_2024_2887_Fig1_HTML.jpg

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