研究动态
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与铜释放相关的长链非编码RNA (lncRNA) 可能预测乳腺癌的预后和治疗敏感性。

Cuproptosis-related lncRNAs potentially predict prognosis and therapy sensitivity of breast cancer.

发表日期:2023
作者: Xiwen Wu, Ying Zhang, Gehao Liang, Huizhen Ye
来源: Frontiers in Pharmacology

摘要:

背景:铜容性相关的长链非编码RNA (lncRNA) 调节各种癌症的生物学功能。然而,铜容性相关的lncRNA在乳腺癌中的作用尚不清楚。本研究旨在探讨铜容性相关的lncRNA在乳腺癌中的生物学功能和临床应用。方法:采用癌症基因组图谱 (TCGA) 数据库和GSE20685数据集对铜容性相关的lncRNA进行筛选。利用克隆形成和CCK-8试剂盒实验检测铜容性相关的lncRNA的增殖功能,利用创伤愈合、迁移和侵袭实验检测铜容性相关的lncRNA在乳腺癌中的转移调节。最后,使用LASSO Cox回归分析构建一个预测性的铜容性相关的lncRNA模型,以检测其对传统治疗(内分泌治疗、化疗和放疗)和新疗法 (PARP和CDK4/6抑制剂) 的生存和敏感性。结果:本研究筛选出与乳腺癌患者生存相关的六个铜容性相关的lncRNA。生物功能实验表明,铜容性相关的lncRNA在调节乳腺癌细胞增殖和转移中起着重要作用。最后,我们应用六个铜容性相关的lncRNA模型将患者分为高风险组和低风险组。高风险组患者的生存率较低 (p < 0.001),对化疗、内分泌治疗和放疗的敏感性较低。与高风险患者相比,低风险患者表达较低的CDK4/6抑制剂耐药标志物 (CCNE1, E2F1, 和E2F2) 和PARP抑制剂耐药标志物 (BRCA1/BRCA2),这表明低风险组患者更适合PARP抑制剂和CDK4/6抑制剂的应用。结论:铜容性相关的lncRNA在调节乳腺癌的生物学功能方面起着重要作用,并有潜力预测乳腺癌对各种治疗方法的预后和敏感性。版权所有 © 2023 Wu, Zhang, Liang和Ye.
Background: Cuproptosis-related lncRNAs regulate the biological functions of various cancers. However, the role of cuproptosis-related lncRNAs in breast cancer remains unclear. In this study, we investigated the biological functions and clinical applications of cuproptosis-related lncRNAs in breast cancer. Methods: The Cancer Genome Atlas (TCGA) database and the GSE20685 dataset were used for screening cuproptosis-related lncRNAs. Colony formation and CCK-8 kit assays were performed for detecting the proliferative function of cuproptosis-related lncRNAs, whereas wound healing, migration, and invasion assays were performed for detecting the metastatic regulation of cuproptosis-related lncRNAs in breast cancer. Finally, a prognostic cuproptosis-related lncRNA model was constructed using LASSO Cox regression analysis for detecting survival and sensitivity to conventional treatment (endocrine therapy, chemotherapy, and radiotherapy) and novel therapy (PARP and CDK4/6 inhibitors). Results: In this study, we screened six cuproptosis-related lncRNAs associated with the survival of patients with breast cancer. Biofunctional experiments indicated that cuproptosis-related lncRNAs play essential roles in regulating the proliferation and metastasis of breast cancer cells. Finally, we applied a model of six cuproptosis-related lncRNAs to classify the patients into high- and low-risk groups. High-risk group patients exhibited worse survival rates (p < 0.001) and lower sensitivity to chemotherapy, endocrine therapy, and radiation therapy. Compared with high-risk patients, low-risk patients exhibited a lower expression of CDK4/6 inhibitor-resistant biomarkers (CCNE1, E2F1, and E2F2) and PARP inhibitor-resistant biomarkers (BRCA1/BRCA2), indicating that patients in the low-risk group were more suitable for PARP inhibitor and CDK4/6 inhibitor application. Conclusion: Cuproptosis-related lncRNAs are essential for regulating the biological functions of breast cancer, and they have the potential to predict prognosis and sensitivity of breast cancer to various therapies.Copyright © 2023 Wu, Zhang, Liang and Ye.