环状 RNA 0027599 通过海绵吸附 miR-21-5p 提升胃癌进展过程中 RUNX1 的表达。
Circ_0027599 elevates RUNX1 expression via sponging miR-21-5p on gastric cancer progression.
机构信息
The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
出版信息
Eur J Clin Invest. 2021 Nov;51(11):e13592. doi: 10.1111/eci.13592. Epub 2021 May 25.
BACKGROUND
Increasing evidence has shown that circular RNAs (circRNAs) serve as vital regulators in tumour progression. In this study, we focused on the functions of circ_0027599 in gastric cancer (GC) progression.
METHODS
The levels of circ_0027599, runt-related transcription factor 1 (RUNX1) mRNA and microRNA-21-5p (miR-21-5p) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The protein levels of RUNX1, E-Cadherin, vimentin and N-Cadherin were measured by Western blot assay. Cell viability, colony formation, metastasis and cell cycle process were evaluated by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, transwell assay and flow cytometry analysis, respectively. The interaction between circ_0027599 and miR-21-5p and the interaction between miR-21-5p and RUNX1 were verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The role of circ_0027599 in tumour growth in vivo was investigated by murine xenograft model assay.
RESULTS
Circ_0027599 and RUNX1 were downregulated in GC tissues and cells. Circ_0027599 level was associated with the overall survival of GC patients. Circ_0027599 or RUNX1 overexpression inhibited GC cell viability, colony formation, migration, invasion and cell cycle process in vitro. For mechanism analysis, circ_0027599 positively regulated RUNX1 expression via functioning as the sponge for miR-21-5p. RUNX1 inhibition reversed circ_0027599 overexpression mediated malignant behaviours of GC cells. Moreover, circ_0027599 overexpression repressed tumour growth in vivo.
CONCLUSION
Circ_0027599 overexpression repressed GC progression via modulation of miR-21-5p/RUNX1 axis, which might illumine a novel therapeutic target for GC.
背景
越来越多的证据表明，环状 RNA（circRNAs）在肿瘤进展中充当重要的调节因子。在本研究中，我们专注于环状 RNA_0027599 在胃癌（GC）进展中的功能。
方法
通过实时定量聚合酶链反应（qRT-PCR）检测环状 RNA_0027599、 runt 相关转录因子 1（RUNX1）mRNA 和 microRNA-21-5p（miR-21-5p）的水平。通过 Western blot 检测 RUNX1、E-钙黏蛋白、波形蛋白和 N-钙黏蛋白的蛋白水平。通过细胞计数试剂盒-8（CCK-8）检测、集落形成检测、Transwell 检测和流式细胞术分析分别评估细胞活力、集落形成、转移和细胞周期过程。通过双荧光素酶报告基因检测和 RNA 免疫沉淀（RIP）检测验证环状 RNA_0027599 与 miR-21-5p 之间的相互作用以及 miR-21-5p 与 RUNX1 之间的相互作用。通过小鼠异种移植模型实验研究环状 RNA_0027599 在体内肿瘤生长中的作用。
结果
环状 RNA_0027599 和 RUNX1 在 GC 组织和细胞中下调。环状 RNA_0027599 水平与 GC 患者的总生存期相关。体外过表达环状 RNA_0027599 或 RUNX1 抑制 GC 细胞活力、集落形成、迁移、侵袭和细胞周期过程。对于机制分析，环状 RNA_0027599 通过作为 miR-21-5p 的海绵正向调节 RUNX1 表达。RUNX1 抑制逆转了环状 RNA_0027599 过表达介导的 GC 细胞恶性行为。此外，环状 RNA_0027599 过表达抑制体内肿瘤生长。
结论
环状 RNA_0027599 通过调节 miR-21-5p/RUNX1 轴抑制 GC 进展，这可能为 GC 提供新的治疗靶点。
Zotero 插件