Long Non-coding RNA ASNR Targeting miR-519e-5p Promotes Gastric Cancer Development by Regulating FGFR2

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.

FGFR families: biological functions and therapeutic interventions in tumors

“…MiR‐381‐3p, miR‐494, miR‐5701, and miR‐519e‐5p also directly target FGFR2 to inhibit its expression and gastric cancer progression, while methyl‐CpG‐binding domain protein 1 and histone deacetylase 3 bind to form a complex that inhibits miR‐5701 expression, thereby restoring FGFR2 levels 219–221 . Long noncoding RNA (lncRNA) ASNR also competitively inhibits miR‐519e‐5p 222 . FGFR2 has been reported to mediate immune tolerance in colorectal cancer cells by inducing PD‐L1 expression through the JAK/STAT3 pathway 223 .…”

Clinical value assessment for serum hsa_tsr013526 in the diagnosis of gastric carcinoma

“…Missense mutations in the FGFR2 gene occur in endometrial cancer, cervical cancer, BC, LC, and GC. The amplified FGFR2 induces activation of the FGFR2 signaling pathway, 37 which downregulates TSP4 via the PI3K‐AKT–mTOR pathway to promote proliferation, invasion, and migration of GC cells, and to inhibit apoptosis, thus exacerbating the progression of GC 38 . According to the principle of interaction between tsRNAs and mRNAs, the levels of tsRNAs should exhibit opposite trends to those of their target genes.…”

Epithelial-mesenchymal transition-related long noncoding RNAs in gastric carcinoma

“…LncASNR (apoptosis suppressing-non-coding RNA) inhibits the expression of miR-519e-5p but up-regulates fibroblast growth factor receptor 2 (FGFR2). As a receptor for FGF, FGFR2 can deliver the FGF signal to RAS-ERK and PI3K-AKT signal cascades, facilitating EMT-related migration and invasion of GC cells ( Chen Z. et al, 2021 ). Overexpression of lncRNA HLA complex group 18 (HCG18) induced by hepatocyte nuclear factor 1 homeobox A (HNF1A) promotes GC progression by competitively binding to miR-152-3p and up-regulating DNAJB12.…”