Wu Xiwen, Zhang Ying, Liang Gehao, Ye Huizhen
Department of Clinical Nutrition, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Staff and Faculty Clinic, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Front Pharmacol. 2023 Jul 17;14:1199883. doi: 10.3389/fphar.2023.1199883. eCollection 2023.
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. 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). 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 ( < 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 (/), indicating that patients in the low-risk group were more suitable for PARP inhibitor and CDK4/6 inhibitor application. 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.
铜死亡相关长链非编码RNA(lncRNAs)调节多种癌症的生物学功能。然而,铜死亡相关lncRNAs在乳腺癌中的作用仍不清楚。在本研究中,我们调查了铜死亡相关lncRNAs在乳腺癌中的生物学功能及临床应用。利用癌症基因组图谱(TCGA)数据库和GSE20685数据集筛选铜死亡相关lncRNAs。进行集落形成实验和CCK-8试剂盒检测以检测铜死亡相关lncRNAs的增殖功能,而进行伤口愈合、迁移和侵袭实验以检测铜死亡相关lncRNAs对乳腺癌转移的调控作用。最后,使用LASSO Cox回归分析构建了一个与铜死亡相关的lncRNA预后模型,用于检测生存情况以及对传统治疗(内分泌治疗、化疗和放疗)和新疗法(PARP和CDK4/6抑制剂)的敏感性。在本研究中,我们筛选出了六种与乳腺癌患者生存相关的铜死亡相关lncRNAs。生物功能实验表明,铜死亡相关lncRNAs在调节乳腺癌细胞的增殖和转移中起重要作用。最后,我们应用一个包含六种铜死亡相关lncRNAs的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差(<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,低风险患者中CDK4/6抑制剂耐药生物标志物(CCNE1、E2F1和E2F2)和PARP抑制剂耐药生物标志物(/)的表达较低,这表明低风险组患者更适合应用PARP抑制剂和CDK4/6抑制剂。铜死亡相关lncRNAs对于调节乳腺癌的生物学功能至关重要,并且它们具有预测乳腺癌预后和对各种疗法敏感性的潜力。