Department of General Surgery, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
Eur Rev Med Pharmacol Sci. 2017 Sep;21(18):4071-4078.
The aberrant expression of microRNAs (miRNAs) has been observed in various types of cancer. Recently, miR-802 was found to play important role in tumor progression. However, the function of miR-802 in gastric cancer (GC) remains unknown. The aim of the present study was to investigate biological effects and underlying mechanisms of miR-802 in GC.
Quantitative RT-PCR was performed to evaluate the expression level of miR-802 in GC tissues and cell lines. The in vitro cell proliferation was measured using the MTT method. Cell invasion and migration assays were performed using the transwell assay. The effects of miR-802 on tumor growth were examined using a GC xenograft model. Flow cytometry method was used to detect the effect of miR-802 in apoptosis of GC cells. Targets of miR-802 were predicted using bioinformatics and validated using luciferase reporter and Western blot analyses.
The results showed that miR-802 was significantly down-regulated in GC tissues and cell lines. The enforced expression of miR-802 induced growth suppression and apoptosis of GC cells. Moreover, miR-802 overexpression suppressed the migration and invasion of GC cells. Bioinformatics analysis predicted that the RAB23 was a potential target gene of miR-802. The results of luciferase reporter assay demonstrated that miR-802 could directly target RAB23. Additionally, in vivo analysis, the xenograft mouse model also confirmed the suppressive effects of miR-802 on tumor growth.
Our results are the first to demonstrate the tumor-suppressive role of miR-802 in GC. The identification of miR-802 and its novel target RAB23 will be valuable in developing therapeutic applications for GC.
已观察到 microRNAs (miRNAs) 的异常表达存在于各种类型的癌症中。最近，发现 miR-802 在肿瘤进展中发挥重要作用。然而，miR-802 在胃癌 (GC) 中的功能仍不清楚。本研究旨在探讨 miR-802 在 GC 中的生物学作用和潜在机制。
通过定量 RT-PCR 评估 miR-802 在 GC 组织和细胞系中的表达水平。使用 MTT 法测量体外细胞增殖。使用 Transwell 测定法进行细胞侵袭和迁移测定。使用 GC 异种移植模型检查 miR-802 对肿瘤生长的影响。使用流式细胞术方法检测 miR-802 对 GC 细胞凋亡的影响。使用生物信息学预测 miR-802 的靶标，并通过荧光素酶报告和 Western blot 分析进行验证。
结果表明，miR-802 在 GC 组织和细胞系中显著下调。miR-802 的强制表达诱导 GC 细胞生长抑制和凋亡。此外，miR-802 过表达抑制 GC 细胞的迁移和侵袭。生物信息学分析预测 RAB23 是 miR-802 的潜在靶基因。荧光素酶报告测定的结果表明，miR-802 可以直接靶向 RAB23。此外，体内分析，异种移植小鼠模型也证实了 miR-802 对肿瘤生长的抑制作用。
我们的研究结果首次证明了 miR-802 在 GC 中的肿瘤抑制作用。鉴定 miR-802 及其新型靶标 RAB23 将有助于开发 GC 的治疗应用。
