环状 RNA1 影响胃癌细胞的增殖和迁移。

CircHN1 affects cell proliferation and migration in gastric cancer.

机构信息

Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.

Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Gansu, China.

出版信息

J Clin Lab Anal. 2020 Oct;34(10):e23433. doi: 10.1002/jcla.23433. Epub 2020 Jul 1.

BACKGROUND

Increasing evidence indicates that circular RNAs (circRNAs) are dysregulated in human cancers. The biological roles of circRNAs in gastric cancer (GC) have not been well-characterized.

METHODS

The GEO database was used to analyze circRNA expression profile in GC. The expression level of target circRNA in tumor tissues and adjacent non-tumor tissues was detected by reverse transcription-quantitative PCR. Gene transfection was used to manipulate the expression of circRNAs. The biological roles of circRNAs in cell proliferation, migration, and invasion were determined by cell counting, colony formation, transwell migration, Matrigel invasion, and mouse xenograft tumor assays. The interactions between circRNAs and miRNAs were verified by RNA immunoprecipitation and luciferase reporter assays.

RESULTS

We found that circHN1 was upregulated in GC tissues and cell lines compared to adjacent non-tumor tissues and normal gastric epithelial cells. Additionally, circHN1 silencing significantly promoted GC cell growth, colony formation, migration, and invasion, whereas circHN1 overexpression had the opposite effects. CircHN1 overexpression also suppressed gastric cancer growth in the mouse xenograft tumor model. CircHN1 was mainly localized in the cytoplasm of GC cells and could bind to AGO2. MiR-1248 and miR-375 were predicted to interact with circHN1 by bioinformatic analyses. MiR-1248 and miR-375 overexpression inhibited the activity of the circHN1 luciferase reporter.

CONCLUSION

CircHN1 is aberrantly expressed in GC and affects the proliferation and migration of gastric cancer cells by acting as miRNA sponge.

背景

越来越多的证据表明，环状 RNA（circRNA）在人类癌症中失调。circRNA 在胃癌（GC）中的生物学作用尚未得到很好的描述。

方法

使用 GEO 数据库分析 GC 中 circRNA 的表达谱。通过逆转录定量 PCR 检测肿瘤组织和相邻非肿瘤组织中靶 circRNA 的表达水平。通过基因转染来操纵 circRNA 的表达。通过细胞计数、集落形成、Transwell 迁移、Matrigel 侵袭和小鼠异种移植肿瘤测定来确定 circRNA 在细胞增殖、迁移和侵袭中的作用。通过 RNA 免疫沉淀和荧光素酶报告基因测定验证 circRNA 和 miRNA 之间的相互作用。

结果

我们发现与相邻非肿瘤组织和正常胃上皮细胞相比，circHN1 在 GC 组织和细胞系中上调。此外，circHN1 沉默显著促进 GC 细胞生长、集落形成、迁移和侵袭，而 circHN1 过表达则产生相反的效果。circHN1 过表达也抑制了小鼠异种移植肿瘤模型中的胃癌生长。circHN1 主要定位于 GC 细胞的细胞质中，并能与 AGO2 结合。生物信息学分析预测 miR-1248 和 miR-375 与 circHN1 相互作用。miR-1248 和 miR-375 的过表达抑制了 circHN1 荧光素酶报告基因的活性。