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Updated: Jun 22, 2025
Combined Conditional Knockdown and Adapted Sphere Formation Assay to Study a Stemness-Associated Gene of Patient-derived Gastric Cancer Stem Cells
Published on: May 9, 2020
lncRNA FGD5-AS1 is required for gastric cancer proliferation by inhibiting cell senescence and ROS production via
Shanshan Qin1,2,3, Yue Liu4, Xiangang Zhang4
1Department of Stomatology, Taihe Hospital and Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, 442000, China. qinss77@163.com.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
FGD5-AS1, a highly abundant long non-coding RNA, promotes gastric cancer (GC) progression by stabilizing the YBX1 protein, inhibiting cell senescence and ROS production. Its overexpression is linked to poor GC survival and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) typically exhibit low expression, limiting their biological roles.
- FGD5-AS1 is a high-expression lncRNA with an unclear non-cegosomal RNA (non-ceRNA) function in cancer.
Purpose of the Study:
- To investigate the biological function and molecular mechanism of FGD5-AS1 in gastric cancer (GC).
- To explore the relationship between FGD5-AS1, ZEB1, and epithelial-mesenchymal transition (EMT) signaling.
Main Methods:
- RNA sequencing (RNA-seq) and chromatin immunoprecipitation (ChIP) assays to identify ZEB1-regulated lncRNAs.
- RNA pulldown, RNA immunoprecipitation (RIP), and rescue assays to elucidate FGD5-AS1's molecular mechanisms in GC.
Main Results:
- FGD5-AS1 is transcriptionally activated by ZEB1 and associated with EMT signaling.
- Overexpression of FGD5-AS1 correlates with lymph node metastasis and poor GC survival.
- FGD5-AS1 knockdown inhibits GC proliferation, enhances cisplatin sensitivity, and induces cell senescence and DNA damage.
- FGD5-AS1 binds to YBX1, prolonging its half-life and promoting GC by repressing senescence and ROS production.
Conclusions:
- FGD5-AS1 is a ZEB1-regulated, high-abundance lncRNA that promotes GC progression.
- FGD5-AS1 enhances GC by inhibiting cell senescence and ROS production via YBX1 stabilization.
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