Yang Fan, Ren Yue, Qi Dongmei, Liu Xi, Xie Jing
Department of Ophthalmology, Southwest Hospital, The Third Military Medical University (Army Medical University), Chongqing, P.R. China.
Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, P.R. China.
J Cancer. 2025 Jan 1;16(2):460-469. doi: 10.7150/jca.101823. eCollection 2025.
Uveal melanoma (UM) has emerged as one of the most common primary intraocular malignant tumors worldwide. Long non-coding RNAs (lncRNAs) are increasingly recognized as decisive factors in the progression and metastasis of UM, involving in epithelial-mesenchymal transition (EMT) of UM. We conducted a comprehensive analysis of lncRNAs closely associated with EMT-related genes in the TCGA UM cohort, identifying 961 EMT-related lncRNAs. Through univariate COX analysis, we identified 9 survival-related EMT-related lncRNAs (sER-lncRNAs), further establishing an EMT-related risk scoring model (ER-RSM) with two sER-lncRNAs (ZNF667-AS1 and AP005121.1) identified by multivariate COX analysis. Through this ER-RSM, low-risk UM patients achieved better overall survival than high-risk UM patients. AP005121.1 was positively correlated with higher stage and M staging in UM patients, while ZNF667-AS1 was positively correlated with earlier stage, T, and M staging in UM patients. , AP005121.1 expression was higher in UM tumor tissues and cell lines than in adjacent normal tissues and human retinal pigment epithelial cells, whereas ZNF667-AS1 expression showed the opposite pattern. siR-AP005121.1 significantly inhibited migration and invasion ability of UM cells and suppressed the EMT pathway, while siR-ZNF667-AS1 promoted migration and invasion of UM cells and activated the EMT pathway. In this study, we screened sER-lncRNAs and constructed an ER-RSM to investigate the relationship between sER-lncRNAs and prognosis and clinical staging of UM. Additionally, we validated the expression of sER-lncRNAs in UM clinical samples and cell lines. The ER-RSM may provide potential key insights for the diagnosis and therapeutic intervention of UM patients.
葡萄膜黑色素瘤（UM）已成为全球最常见的原发性眼内恶性肿瘤之一。长链非编码RNA（lncRNAs）越来越被认为是UM进展和转移的决定性因素，参与UM的上皮-间质转化（EMT）。我们对TCGA UM队列中与EMT相关基因密切相关的lncRNAs进行了综合分析，鉴定出961个与EMT相关的lncRNAs。通过单因素COX分析，我们鉴定出9个与生存相关的EMT相关lncRNAs（sER-lncRNAs），进一步构建了一个由多因素COX分析鉴定出的两个sER-lncRNAs（ZNF667-AS1和AP005121.1）组成的EMT相关风险评分模型（ER-RSM）。通过这个ER-RSM，低风险UM患者的总生存期比高风险UM患者更好。AP005121.1与UM患者的更高分期和M分期呈正相关，而ZNF667-AS1与UM患者的更早分期、T分期和M分期呈正相关。AP005121.1在UM肿瘤组织和细胞系中的表达高于相邻正常组织和人视网膜色素上皮细胞，而ZNF667-AS1的表达则呈现相反的模式。siR-AP005121.1显著抑制UM细胞的迁移和侵袭能力，并抑制EMT途径，而siR-ZNF667-AS1促进UM细胞的迁移和侵袭并激活EMT途径。在本研究中，我们筛选了sER-lncRNAs并构建了ER-RSM，以研究sER-lncRNAs与UM预后和临床分期之间的关系。此外，我们验证了sER-lncRNAs在UM临床样本和细胞系中的表达。ER-RSM可能为UM患者的诊断和治疗干预提供潜在的关键见解。
