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Long Non-coding RNA ASNR Targeting miR-519e-5p Promotes Gastric Cancer Development by Regulating FGFR2
Zihao Chen1,2, Yong Li2, Bibo Tan2
1Graduate School of Hebei Medical University, Shijiazhuang, China.
Abstract:
Gastric cancer (GC), as a common gastrointestinal tumor, is an important cause of death from cancer all around the world. Long non-coding RNAs (lncRNAs), a novel class of transcripts, have attracted great attention of researchers. However, the mechanisms of the clinical significance of most lncRNAs in human cancer are mainly undocumented. This research desires to explore the clinical significance, biological function, and mechanism of Lnc_ASNR (apoptosis suppressing-non-coding RNA) in GC. Cell proliferation, cell cycle, cell migration, and invasion abilities were respectively determined by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), flow cytometry, wound healing, and Transwell assay (Sigma-Aldrich, St. Louis, MO, United States). The association of Lnc_ASNR, miR-519e-5p, and fibroblast growth factor receptor 2 (FGFR2) was evaluated via luciferase reporter experiments. The tumor xenograft assay was conducted to confirm the results of cell experiments. High expressed Lnc_ASNR was detected in both GC cells and tissues using qRT-PCR. Downregulated Lnc_ASNR could reduce proliferation, migration, and invasion in GC cells, while upregulated Lnc_ASNR could promote the cell proliferation, migration, and invasion. Moreover, the effect of Lnc_ASNR on migration and invasion ability is closely related to epithelial-mesenchymal transition (EMT). The bioinformatics analysis, luciferase assay, and Western blot demonstrated that Lnc_ASNR inhibited miR-519e-5p expression but increased FGFR2 expression. Lnc_ASNR and FGFR2 were both targeted to miR-519e-5p, and they were negatively correlated with the expression of miR-519e-5p. All investigations indicated that Lnc_ASNR functioned as a ceRNA targeting miR-519e-5p and facilitated GC development by regulating the pathway of miR-519e-5p/FGFR2.
Insights
Long non-coding RNA (lncRNA) Lnc_ASNR promotes gastric cancer (GC) progression by inhibiting miR-519e-5p and upregulating FGFR2. This ceRNA mechanism drives GC development and epithelial-mesenchymal transition (EMT).
Area of Science:
- Molecular Oncology
- Cancer Biology
- RNA Therapeutics
Background:
- Gastric cancer (GC) is a leading cause of cancer mortality worldwide.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer, but their specific functions in GC remain largely unexplored.
- Understanding the molecular mechanisms underlying GC progression is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the clinical significance, biological function, and underlying mechanism of Lnc_ASNR (apoptosis suppressing-non-coding RNA) in gastric cancer.
- To elucidate the regulatory network involving Lnc_ASNR, miR-519e-5p, and fibroblast growth factor receptor 2 (FGFR2) in GC.
- To determine the role of Lnc_ASNR in GC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to assess Lnc_ASNR expression in GC tissues and cells.
- Cell-based assays including MTT, flow cytometry, wound healing, and Transwell assays to evaluate proliferation, cell cycle, migration, and invasion.
- Luciferase reporter assays, bioinformatics analysis, and Western blot to confirm interactions between Lnc_ASNR, miR-519e-5p, and FGFR2.
Main Results:
- Lnc_ASNR was significantly upregulated in GC tissues and cells.
- Downregulation of Lnc_ASNR suppressed GC cell proliferation, migration, and invasion, while its upregulation promoted these processes.
- Lnc_ASNR acted as a competing endogenous RNA (ceRNA), inhibiting miR-519e-5p and consequently increasing FGFR2 expression, thereby promoting GC development and EMT.
Conclusions:
- Lnc_ASNR plays a critical oncogenic role in gastric cancer progression.
- The miR-519e-5p/FGFR2 pathway is a key mechanism through which Lnc_ASNR exerts its effects on GC.
- Lnc_ASNR represents a potential therapeutic target for gastric cancer treatment.
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