Background: Enhancer RNAs (eRNAs), a subclass of long non-coding RNAs transcribed from enhancer regions, have emerged as dynamic regulators of gene expression, tumor progression, and therapeutic response. In gliomas, their biological and clinical significance is only recently being elucidated. This systematic review aimed to synthesize current evidence regarding the role of eRNAs in gliomagenesis, chemoresistance, and prognosis. Methods: We conducted a systematic review following PRISMA 2020 guidelines. PubMed/MEDLINE and Scopus databases were searched on September 2025 using a predefined strategy. Eligible studies included clinical or pre-clinical analyses of eRNAs in gliomas, reporting associations with tumorigenicity, survival, or resistance to temozolomide (TMZ). Risk of bias was assessed using ROBINS-I (Version 2), and findings were qualitatively synthesized. Results: From 26 retrieved records, 10 studies were included, encompassing 22 unique eRNAs. Two studies demonstrated that TMZR1-eRNA and LINC02454* modulate TMZ sensitivity by regulating STAT3, SORBS2, and DDR1 pathways. Seven studies evaluated prognostic implications: 12 eRNAs (e.g., AC003092.1, CYP1B1-AS1, CRNDE) were consistently associated with poor survival, while seven (e.g., LINC00844, ENSR00000260547) correlated with favorable outcomes, particularly in low-grade gliomas. One mechanistic study showed that HOXDeRNA directly promotes gliomagenesis by displacing PRC2 repression at key transcription factor promoters and activating oncogenic super-enhancers. Conclusions: eRNAs are not passive transcriptional by-products but active modulators of glioma biology. They influence tumor initiation, therapeutic resistance, and survival outcomes, underscoring their potential as prognostic biomarkers and therapeutic targets. Future research should validate these findings in larger clinical cohorts and explore strategies for eRNA-directed therapies in precision neuro-oncology.
**背景：** 增强子RNA是一类从增强子区域转录的长链非编码RNA亚型，已成为基因表达、肿瘤进展和治疗反应的动态调控因子。在胶质瘤中，其生物学和临床意义直到最近才被阐明。本系统综述旨在综合当前关于eRNA在胶质瘤发生、化疗耐药和预后中作用的证据。 **方法：** 我们遵循PRISMA 2020指南进行了系统综述。于2025年9月使用预设策略检索了PubMed/MEDLINE和Scopus数据库。符合条件的研究包括胶质瘤中eRNA的临床或临床前分析，并报告了其与致瘤性、生存期或替莫唑胺耐药性的关联。使用ROBINS-I（第2版）评估偏倚风险，并对结果进行定性综合。 **结果：** 从检索到的26篇文献中，纳入了10项研究，共涉及22种独特的eRNA。两项研究表明，TMZR1-eRNA和LINC02454*通过调控STAT3、SORBS2和DDR1通路来调节TMZ敏感性。七项研究评估了预后意义：12种eRNA（如AC003092.1、CYP1B1-AS1、CRNDE）始终与不良生存期相关，而七种eRNA（如LINC00844、ENSR00000260547）则与良好预后相关，尤其在低级别胶质瘤中。一项机制研究表明，HOXDeRNA通过置换关键转录因子启动子处的PRC2抑制并激活致癌超级增强子，直接促进胶质瘤发生。 **结论：** eRNA并非被动的转录副产物，而是胶质瘤生物学的主动调节因子。它们影响肿瘤发生、治疗耐药和生存结局，凸显了其作为预后生物标志物和治疗靶点的潜力。未来的研究应在更大的临床队列中验证这些发现，并探索精准神经肿瘤学中eRNA导向的治疗策略。
Unveiling Enhancer RNAs in Gliomas: A Systematic Review and Qualitative Synthesis
肿瘤(癌症)患者之家