miR-877-5p Suppresses Gastric Cancer Cell Proliferation Through Targeting FOXM1
miR-877-5p Suppresses Gastric Cancer Cell Proliferation Through Targeting FOXM1
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miR-877-5p 通过靶向 FOXM1 抑制胃癌细胞增殖
DOI：
10.2147/ott.s251916
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Xiao, Qiang
中科院分区：
文献类型：
--
作者：
Wu, Kun;Yu, Zhu;Xiao, Qiang
目的：miR-877-5p已被报道为多种癌症的肿瘤抑制因子。然而，它在胃癌中的作用尚不清楚。因此，本研究的目的是阐明miR-877-5p在胃癌发生发展中的功能及其潜在的分子机制。材料和方法：我们首先利用Gene expression Omnibus （GEO）数据库分析miR-877-5p的表达，并通过实时定量PCR （real-time quantitative PCR, qRT-PCR）检测其在胃癌和胃上皮细胞中的表达。然后我们评估了miR-877-5p在胃癌增殖、凋亡和细胞周期中的作用。通过生物信息学分析预测miR-877-5p靶向的基因，并通过双荧光素酶试验证实。随后，我们进行了挽救试验来验证miR-877-5p对胃癌生长的影响是否依赖于所提出的靶基因。结果：根据GEO和qRT-PCR分析，胃癌中miR-877-5p水平低于对照组。过表达miR-877-5p显著抑制细胞生长和细胞周期进程，促进细胞凋亡。此外，叉头盒M1 （FOXM1）被预测为miR-877-5p的靶标，其过表达减弱了miR-877-5p上调对胃癌细胞的抑制作用。结论：我们的研究结果表明miR-877-5p/FOXM1轴在胃癌进展中发挥重要作用，同时提示miR-877-5p是胃癌新的潜在治疗靶点。
Purpose: miR-877-5p has been reported as a tumor suppressor in multiple cancers. Its role in gastric cancer, however, remains unclear. Hence, the purpose of this study was to elucidate the function, and underlying molecular mechanism, of miR-877-5p in the development of gastric cancer.Materials and Methods: We first analyzed miR-877-5p expression using the Gene Expression Omnibus (GEO) database and detected its expression in gastric cancer and gastric epithelial cells via real-time quantitative PCR (qRT-PCR). We then assessed the role of miR-877-5p in gastric cancer proliferation, apoptosis, and cell cycling. The gene targeted by miR-877-5p was predicted by bioinformatic analysis and confirmed by dual luciferase assay. Subsequently, rescue assays were carried out to validate whether the miR-877-5p effects on gastric cancer growth are dependent on the proposed target gene.Results: miR-877-5p levels were lower in gastric cancer than in controls, based on the GEO and qRT-PCR analyses. Overexpression of miR-877-5p significantly inhibited cell growth and cell cycle progression, whereas it promoted apoptosis. Furthermore, forkhead box M1 (FOXM1) was predicted as a target of miR-877-5p, the overexpression of which diminished the suppressive effect that upregulation of miR-877-5p had on gastric cancer cells.Conclusion: Our study results indicate that the miR-877-5p/FOXM1 axis plays an important role in gastric cancer progression, while suggesting miR-877-5p as a novel potential therapeutic target for gastric cancer.