Chen Zihao, Li Yong, Tan Bibo, Li Fang, Zhao Qun, Fan Liqiao, Zhang Zhidong, Zhao Xuefeng, Liu Yu, Wang Dong
Graduate School of Hebei Medical University, Shijiazhuang, China.
The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Front Cell Dev Biol. 2021 Jul 9;9:679176. doi: 10.3389/fcell.2021.679176. eCollection 2021.
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 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.
胃癌（GC）作为一种常见的胃肠道肿瘤，是全球癌症死亡的重要原因。长链非编码RNA（lncRNAs）作为一类新型转录本，已引起研究人员的高度关注。然而，大多数lncRNAs在人类癌症中的临床意义机制主要尚未明确。本研究旨在探讨Lnc_ASNR（凋亡抑制非编码RNA）在GC中的临床意义、生物学功能及机制。分别采用3-(4,5)-二甲基噻唑-2,5-二苯基四氮唑溴盐（MTT）、流式细胞术、伤口愈合实验和Transwell实验（美国密苏里州圣路易斯市西格玛奥德里奇公司）测定细胞增殖、细胞周期、细胞迁移和侵袭能力。通过荧光素酶报告基因实验评估Lnc_ASNR、miR-519e-5p和成纤维细胞生长因子受体2（FGFR2）之间的关联。进行肿瘤异种移植实验以证实细胞实验结果。使用qRT-PCR在GC细胞和组织中均检测到Lnc_ASNR高表达。下调Lnc_ASNR可降低GC细胞的增殖、迁移和侵袭能力，而上调Lnc_ASNR则可促进细胞增殖、迁移和侵袭。此外，Lnc_ASNR对迁移和侵袭能力的影响与上皮-间质转化（EMT）密切相关。生物信息学分析、荧光素酶实验和蛋白质免疫印迹表明，Lnc_ASNR抑制miR-519e-5p表达但增加FGFR2表达。Lnc_ASNR和FGFR2均靶向miR-519e-5p，且它们与miR-519e-5p的表达呈负相关。所有研究表明，Lnc_ASNR作为靶向miR-519e-5p的竞争性内源性RNA（ceRNA），通过调节miR-519e-5p/FGFR2通路促进GC进展。
