lncRNA FGD5-AS1 is required for gastric cancer proliferation by inhibiting cell senescence and ROS production via stabilizing YBX1

• Published in: Journal of experimental & clinical cancer research Vol. 43; no. 1; pp. 188 - 17
• Main Authors: Qin, Shanshan, Liu, Yue, Zhang, Xiangang, Huang, Pan, Xia, Lingyun, Leng, Weidong, Li, Dandan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05.07.2024; BioMed Central; BMC
• Subjects: Analysis; Animals; Apoptosis; Biomarkers; Cancer; Cancer therapies; Cell growth; Cell Line, Tumor; Cell Proliferation; Cell senescence; Cellular Senescence; Chromatin; Development and progression; Epithelial-Mesenchymal Transition; Female; Gastric cancer; Gene Expression Regulation, Neoplastic; Genes; Genetic transcription; Guanine Nucleotide Exchange Factors; Humans; Lymphatic system; Male; Medical prognosis; Messenger RNA; Metastasis; Mice; Protein binding; Proteins; Reactive Oxygen Species - metabolism; RNA polymerase; RNA sequencing; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA-protein interaction; ROS; Senescence; Stem cells; Stomach cancer; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Transcription factors; Transcriptional regulation; Y-Box-Binding Protein 1 - genetics; Y-Box-Binding Protein 1 - metabolism; China; Cell senescence; RNA-protein interaction; Transcriptional regulation; Gastric cancer; ROS
• DOI: 10.1186/s13046-024-03103-x
• ISSN: 1756-9966; 0392-9078

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.