Piergentili Roberto, Sechi Stefano, De Paola Lina, Zaami Simona, Marinelli Enrico
Institute of Molecular Biology and Pathology, Italian National Research Council (CNR-IBPM), 00185 Rome, Italy.
Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, 00161 Rome, Italy.
Noncoding RNA. 2025 Apr 30;11(3):34. doi: 10.3390/ncrna11030034.
Competing endogenous RNAs (ceRNA) are molecules that compete for the binding to a microRNA (miR). Usually, there are two ceRNA, one of which is a protein-coding RNA (mRNA), with the other being a long non-coding RNA (lncRNA). The miR role is to inhibit mRNA expression, either promoting its degradation or impairing its translation. The lncRNA can "sponge" the miR, thus impeding its inhibitory action on the mRNA. In their easier configuration, these three molecules constitute a regulatory axis for protein expression. However, each RNA can interact with multiple targets, creating branched and intersected axes that, all together, constitute what is known as a competing endogenous RNA network (ceRNET). In this systematic review, we collected all available data from PubMed about experimentally verified (by luciferase assay) regulatory axes in endometrial cancer (EC), excluding works not using this test; This search allowed the selection of 172 bibliographic sources, and manually building a series of ceRNETs of variable complexity showed the known axes and the deduced intersections. The main limitation of this search is the highly stringent selection criteria, possibly leading to an underestimation of the complexity of the networks identified. However, this work allows us not only to hypothesize possible gap fillings but also to set the basis to instruct artificial intelligence, using adequate prompts, to expand the EC ceRNET by comparing it with ceRNETs of other cancers. Moreover, these networks can be used to inform and guide research toward specific, though still unidentified, axes in EC, to complete parts of the network that are only partially described, or even to integrate low complexity subnetworks into larger more complex ones. Filling the gaps among the existing EC ceRNET will allow physicians to hypothesize new therapeutic strategies that may either potentiate or substitute existing ones. These ceRNETs allow us to easily visualize long-distance interactions, thus helping to select the best treatment, depending on the molecular profile of each patient, for personalized medicine. This would yield higher efficiency rates and lower toxicity levels, both of which are extremely relevant factors not only for patients' wellbeing, but also for the legal, regulatory, and ethical aspects of miR-based innovative treatments and personalized medicine as a whole. This systematic review has been registered in PROSPERO (ID: PROSPERO 2025 CRD420251035222).
竞争性内源性RNA（ceRNA）是一类能够竞争结合微小RNA（miR）的分子。通常情况下，存在两种ceRNA，其中一种是蛋白质编码RNA（mRNA），另一种是长链非编码RNA（lncRNA）。miR的作用是抑制mRNA的表达，促进其降解或损害其翻译过程。lncRNA可以“吸附”miR，从而阻碍其对mRNA的抑制作用。在较为简单的结构中，这三种分子构成了蛋白质表达的调控轴。然而，每种RNA都可以与多个靶点相互作用，形成分支和交叉的轴，这些轴共同构成了所谓的竞争性内源性RNA网络（ceRNET）。在本系统综述中，我们从PubMed收集了所有关于子宫内膜癌（EC）中经实验验证（通过荧光素酶测定）的调控轴的可用数据，排除了未使用该检测方法的研究；通过此次检索，我们筛选出了172篇文献来源，并手动构建了一系列复杂程度各异的ceRNET，展示了已知的轴和推断出的交叉点。此次检索的主要局限性在于选择标准极为严格，可能导致对所确定网络复杂性的低估。然而，这项工作不仅使我们能够推测可能的填补空白之处，还为利用适当的提示指导人工智能通过与其他癌症的ceRNET进行比较来扩展EC的ceRNET奠定了基础。此外，这些网络可用于为针对EC中特定但尚未明确的轴的研究提供信息和指导，以完成仅部分描述的网络部分，甚至将低复杂性子网整合到更大、更复杂的网络中。填补现有EC ceRNET之间的空白将使医生能够推测出新的治疗策略，这些策略可能增强或替代现有的治疗方法。这些ceRNET使我们能够轻松可视化长距离相互作用，从而有助于根据每位患者的分子特征选择最佳治疗方案，实现个性化医疗。这将产生更高的效率和更低的毒性水平，这两个因素不仅对患者的健康极为重要，而且对基于miR的创新治疗和整个个性化医疗的法律、监管和伦理方面也至关重要。本系统综述已在PROSPERO注册（编号：PROSPERO 2025 CRD420251035222）。
