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Circ-SERPINE2 通过海绵吸附 miR-375 并调节 YWHAZ 促进胃癌的发展。

Circ-SERPINE2 promotes the development of gastric carcinoma by sponging miR-375 and modulating YWHAZ.

机构信息

Department of Thyroid and Pancreatic Disease, The Second Hospital of Shandong University, Jinan, China.

Department of Internal Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Cell Prolif. 2019 Jul;52(4):e12648. doi: 10.1111/cpr.12648. Epub 2019 Jun 14.

Abstract

OBJECTIVES

Circular RNAs (circRNAs) exist extensively in the eukaryotic genome. The study aimed to identify the role of hsa_circ_0008365 (Circ-SERPINE2) in gastric carcinoma (GC) cells and its downstream mechanisms.

MATERIALS AND METHODS

Gene Expression Omnibus (GEO) database was applied to screen differentially expressed circRNAs. CircInteractome, TargetScan and miRecords websites were used to predict target relationships. qRT-PCR and RNase R treatment were utilised to detect molecule expression and confirm the existence of circ-SERPINE2. RNA pull-down assay and dual-luciferase reporter assay were performed for interaction between circRNA and miRNA or mRNA. EdU assay, colony formation assay, and flow cytometry for apoptosis and cell cycle detections were utilised to assess cell function. Western blot and immunohistochemistry (IHC) assays were applied for detection of proteins in tissues or cells.

RESULTS

Circ-SERPINE2 and YWHAZ were upregulated, and miR-375 was downregulated in GC tissues and cells. Circ-SERPINE2 and YWHAZ targetedly bound to miR-375. Circ-SERPINE2 promoted cell proliferation and cell cycle progress and inhibited cell apoptosis by sponging miR-375 and regulating YWHAZ expression in vitro. Circ-SERPINE2 repressed solid tumour growth through enhancing miR-375 expression and reducing YWHAZ expression in vivo.

CONCLUSIONS

Circ-SERPINE2 is a novel proliferative promoter through the regulation of miR-375/YWHAZ. Circ-SERPINE2/miR-375/YWHAZ axis might provide a novel therapeutic target of GC.

摘要

目的

环状 RNA(circRNAs)广泛存在于真核基因组中。本研究旨在鉴定 hsa_circ_0008365(Circ-SERPINE2)在胃癌(GC)细胞中的作用及其下游机制。

材料和方法

应用基因表达综合数据库(GEO)筛选差异表达的 circRNAs。CircInteractome、TargetScan 和 miRecords 网站用于预测靶基因关系。qRT-PCR 和 RNase R 处理用于检测分子表达并确认 circ-SERPINE2 的存在。RNA 下拉实验和双荧光素酶报告基因实验用于检测 circRNA 与 miRNA 或 mRNA 之间的相互作用。EdU 实验、集落形成实验和流式细胞术用于检测细胞凋亡和细胞周期。Western blot 和免疫组织化学(IHC)实验用于检测组织或细胞中的蛋白。

结果

GC 组织和细胞中 circ-SERPINE2 和 YWHAZ 上调,miR-375 下调。circ-SERPINE2 和 YWHAZ 靶向结合 miR-375。Circ-SERPINE2 通过海绵吸附 miR-375 和调节 YWHAZ 表达在体外促进细胞增殖、细胞周期进展并抑制细胞凋亡。Circ-SERPINE2 通过增强 miR-375 表达和降低 YWHAZ 表达在体内抑制实体瘤生长。

结论

Circ-SERPINE2 通过调节 miR-375/YWHAZ 成为一种新型增殖促进物。Circ-SERPINE2/miR-375/YWHAZ 轴可能为 GC 提供新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d769/6668981/797582aa8cba/CPR-52-e12648-g001.jpg

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