绝大多数lncRNA的表达丰度较低，这极大地限制了它们的功能范围和影响。作为一种高表达丰度的lncRNA，FGD5-AS1在癌症中的非ceRNA生物学功能尚不清楚。进行RNA-seq研究和染色质免疫沉淀（芯片）测定来鉴定ZEB1调节的lncRNA。通过RNA测序、RNA Pulldown、RNA免疫沉淀实验和救援实验来探索FGD5-AS1在GC中的分子机制。作为细胞中最丰富的lncRNA之一，FGD5-AS1已被证明可以被ZEB1转录激活，因此与上皮间质转化（EMT）信号密切相关。临床分析表明，FGD5-AS1 过表达在临床上与淋巴结转移相关，并预测 GC 患者的生存率较差。功能丧失研究证实，FGD5-AS1 敲低可抑制 GC 增殖，并诱导 GC 细胞顺铂化疗敏感性、细胞衰老和 DNA 损伤。从机制上讲，FGD5-AS1 是一种 YBX1 结合 lncRNA，因为其 mRNA 包含三个可以被 YBX1 识别和结合的相邻结构基序（UAAUCCCA、ACCAGCCU 和 CAGUGAGC）。这种RNA-蛋白质相互作用延长了YBX1蛋白在GC中的半衰期。此外，救援试验表明，FGD5-AS1 通过 YBX1 抑制细胞衰老和 ROS 产生来促进 GC。FGD5-AS1 是一种细胞高丰度 lncRNA，受 ZEB1 转录调控。 FGD5-AS1 过表达通过结合和稳定 YBX1 蛋白来抑制细胞衰老和 ROS 产生，从而促进 GC 进展。© 2024。作者。

The vast majority of lncRNAs have low expression abundance, which greatly limits their functional range and impact. As a high expression abundance lncRNA, FGD5-AS1's non-ceRNA biological function in cancer is unclear.RNA-seq studies and chromatin immunoprecipitation (Chip) assays were performed to identify ZEB1-regulated lncRNAs. RNA sequencing, RNA pulldown, RNA Immunoprecipitation assays, and rescue assays were conducted to explore the molecular mechanisms of FGD5-AS1 in GC.As one of the most abundant lncRNAs in cells, FGD5-AS1 has been shown to be transcriptionally activated by ZEB1, thus closely related to epithelial-mesenchymal transition (EMT) signaling. Clinical analysis showed that FGD5-AS1 overexpression was clinically associated with lymph node metastasis, and predicted poor survival in GC. Loss-of-function studies confirmed that FGD5-AS1 knockdown inhibited GC proliferation and induced cisplatin chemosensibility, cell senescence, and DNA damage in GC cells. Mechanismically, FGD5-AS1 is a YBX1-binding lncRNA due to its mRNA contains three adjacent structural motifs (UAAUCCCA, ACCAGCCU, and CAGUGAGC) that can be recognized and bound by YBX1. And this RNA-protein interaction prolonged the half-life of the YBX1 protein in GC. Additionally, a rescue assay showed that FGD5-AS1 promotes GC by repressing cell senescence and ROS production via YBX1.FGD5-AS1 is a cellular high-abundant lncRNA that is transcriptionally regulated by ZEB1. FGD5-AS1 overexpression promoted GC progression by inhibiting cell senescence and ROS production through binding and stabilizing the YBX1 protein.© 2024. The Author(s).