LINC00519 通过 miR-876-3p/HMGA1 轴调控胃癌细胞的增殖、凋亡、 迁移和侵袭

目的：探讨长基因间非编码RNA 00519（long intergene non-coding RNA 00519，LINC00519）调控miR-876-3p/高迁移 率家族蛋白A1（high mobility group protein A1，HMGA1）轴在胃癌HGC-27细胞的增殖、凋亡、迁移和侵袭中的作用。方法：采用 qPCR检测胃癌细胞 HGC-27 和胃黏膜上皮细胞 GES-1 中 LINC00519 的表达水平。将HGC-27细胞按转染处理分为si-NC、 si-LINC00519、si-LINC00519+anti-miR-NC和si-LINC00519+anti-miR-876-3p组，采用集落形成实验检测细胞克隆形成能力，流式 细胞术检测细胞凋亡和周期分布 ，Transwell 实验检测细胞迁移和侵袭。双荧光素酶报告实验和qPCR验证LINC00519与 miR-876-3p、miR-876-3p与HMGA1之间的相互作用。结果：HGC-27细胞中LINC00519表达较GES-1细胞显著升高（ P<0.05），转染siRNA后si-LINC00519 组 HGC-27细胞中LINC00519的表达水平较si-NC组显著降低（t=47.294 ，P<0.01）。与 si-NC组 比较，si-LINC00519组HGC-27细胞克隆数、迁移侵袭数、S期细胞比例均显著降低（均P<0.01），凋亡率、G0/G1期细胞比例均显著 升高（均 P<0.01）。与si-LINC00519+anti-miR-NC 组比较，si-LINC00519+anti-miR-876-3p组HGC-27 细胞克隆数、迁移侵袭数、 S期细胞比例升高（均P<0.01），凋亡率、G0/G1期细胞比例显著降低（均P<0.01）。LINC00519能够靶向负调控miR-876-3p的表 达，miR-876-3p靶向负调控HMGA1的表达。结论：敲降LINC00519能够通过调控miR-876-3p/HMGA1轴抑制胃癌HGC-27细 胞的增殖、迁移和侵袭，诱导细胞凋亡。

LINC00519 regulates the proliferation, apoptosis, migration and invasion of gastric cancer cells through the miR-876-3p/HMGA1 axis

Objective: To investigate the effect of long intergene non-coding RNA 00519 (LINC00519) on the proliferation, apoptosis, migration and invasion of gastric cancer HGC-27 cells by regulating the miR-876-3p / high mobility group protein A1 (HMGA1) axis. Methods: The expression levels of LINC00519 in gastric cancer HGC-27 cells and gastric mucosal epithelial GES-1 cells were detected by qPCR. HGC-27 cells were divided into si-NC, si-LINC00519, si-LINC00519+anti-miR-NC, and si-LINC00519 + anti-miR1]876-3p groups according to transfection treatment. Colony formation test was applied to detect cell cloning ability; Flow cytometry was used to detect apoptosis and cell cycle distribution; Transwell assay was selected to measure cell migration and invasion. Dual luciferase reporter gene assay and qPCR were applied to confirm the interaction between LINC00519 and miR-876-3p as well as between miR-876-3p and HMGA1. Results: The expression of LINC00519 in HGC-27 cells was significantly higher than that in GES1] 1 cells (P <0.05). After siRNA transfection, the expression level of LINC00519 in HGC-27 cells of the si-LINC00519 group was significantly lower than that of the si-NC group (t=47.294, P<0.01). Compared with the si-NC group, the number of HGC-27 cell clones, the number of migrated and invaded cells, and proportion of S-phase cells in the si-LINC00519 group were significantly decreased (all P<0.01), while the apoptosis rate and the proportion of G0/G1 phase cells were significantly increased (all P <0.01). Compared with the si-LINC00519+anti-miR-NC group, the number of HGC-27 cell clones, the number of migrated and invaded cells, proportion of S-phase cells were significantly increased (all P<0.01), while the apoptosis rate and the proportion of G0/G1 phase cells in the si-LINC00519 + anti-miR-876-3p group were significantly decreased (all P<0.01), LINC00519 could target and negatively regulate miR-876-3p expression. miR-876-3p could target and negatively regulate HMGA1 expression. Conclusion: Knocking down LINC00519 could inhibit the proliferation, migration and invasion of gastric cancer HGC-27 cells and induce apoptosis by regulating the miR-876-3p/HMGA1 axis.