Department of Hand Plastic Surgery, The First People’s Hospital of Linping District, Hangzhou 311199, China.
Department of Oncology, Huaibei People’s Hospital, Huaibei 235000, China.
Aging (Albany NY). 2023 May 19;15(10):4236-4252. doi: 10.18632/aging.204726.
As a novel cell death modality, oxeiptosis is mainly caused by oxidative stress. However, the associations of uterine corpus endometrial carcinoma (UCEC) with oxeiptosis-associated long non-coding RNAs (lncRNAs) are unknown. Here, to identify hub oxeiptosis-associated lncRNAs in UCEC, we collected the data for lncRNAs and gene expression in UCEC from The Cancer Genome Atlas (TCGA) database. Then, a lncRNA risk signature was constructed, and its prognostic value was further evaluated. Finally, the expression levels of hub lncRNA were validated by quantitative RT-PCR analysis. MTT and wounding analyses were also applied to confirm the role of HOXB-AS3 knockdown on UCEC cells. Five lncRNAs associated with oxeiptosis and connected to the prognosis of UCEC were identified, and a risk signature was constructed based on these identified lncRNAs. Our clinical value analyses suggested that the risk signature was closely connected to the overall survival, TNM stage, and grade of UCEC patients. Meanwhile, compared to the conventional clinicopathological characteristics, this risk signature exhibited significantly higher diagnostic accuracy. Moreover, the potential mechanism analysis indicated a close connection of this risk signature to tumor stemness, m6A-related genes, immune cell infiltration, and immune subtypes. Based on the risk scores, we constructed a nomogram. experiments found that was significantly higher expressed in UCEC cells, and the silence of inhibited the proliferation and migration of UCEC cells. In conclusion, using five hub lncRNAs associated with oxeiptosis, we generated a risk signature, which could be applied in the novel therapeutic strategies of UCEC development.
作为一种新型的细胞死亡方式,氧化细胞凋亡主要由氧化应激引起。然而,子宫体子宫内膜癌(UCEC)与氧化细胞凋亡相关的长链非编码 RNA(lncRNA)的关联尚不清楚。在这里,为了确定与氧化细胞凋亡相关的 lncRNA 在 UCEC 中的关键作用,我们从癌症基因组图谱(TCGA)数据库中收集了 UCEC 的 lncRNA 和基因表达数据。然后,构建了 lncRNA 风险特征,并进一步评估了其预后价值。最后,通过定量 RT-PCR 分析验证了关键 lncRNA 的表达水平。还应用 MTT 和划痕分析来确认 HOXB-AS3 敲低对 UCEC 细胞的作用。确定了与氧化细胞凋亡相关且与 UCEC 预后相关的 5 个 lncRNA,并基于这些鉴定的 lncRNA 构建了风险特征。我们的临床价值分析表明,风险特征与 UCEC 患者的总生存率、TNM 分期和分级密切相关。同时,与常规临床病理特征相比,该风险特征表现出明显更高的诊断准确性。此外,潜在机制分析表明,该风险特征与肿瘤干性、m6A 相关基因、免疫细胞浸润和免疫亚型密切相关。基于风险评分,我们构建了一个列线图。实验发现,在 UCEC 细胞中 表达显著上调,沉默 抑制了 UCEC 细胞的增殖和迁移。总之,使用与氧化细胞凋亡相关的五个关键 lncRNA,我们生成了一个风险特征,可以应用于 UCEC 发展的新治疗策略。