环状 RNA 0021087 作为 miR-184 的海绵体，通过吸附 miR-184 和上调 FOSB 表达来抑制胃癌的进展。

Circ_0021087 acts as a miR-184 sponge and represses gastric cancer progression by adsorbing miR-184 and elevating FOSB expression.

机构信息

School of Basic Medicine, Zhengzhou University, Zhengzhou City, China.

Department of Radiology, Zhumadian Central Hospital Affiliated to Huanghuai University, Zhumadian City, China.

出版信息

Eur J Clin Invest. 2021 Nov;51(11):e13605. doi: 10.1111/eci.13605. Epub 2021 Jun 2.

DOI:10.1111/eci.13605

PMID:34076278

Abstract

BACKGROUND

Gastric cancer (GC) ranks third among the causes of cancer-related deaths in the world. Circular RNA hsa_circ_0021087 (circ_0021087) plays a repressive role in GC. Nevertheless, the mechanism by which circ_0021087 constrains GC advancement is unclear.

MATERIALS AND METHODS

Expression patterns of circ_0021087, microRNA (miR)-184 and FBJ murine osteosarcoma viral oncogene homolog B (FOSB) mRNA were assessed by quantitative real-time polymerase chain reaction (RT-qPCR). Gain-of-function experiments were conducted to verify the biological function of circ_0021087 in vitro and in vivo, including cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell and xenograft assays. Protein levels were analysed by Western blotting and immunohistochemistry (IHC). The regulatory mechanism of circ_0021087 was analysed by bioinformatics analysis, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.

RESULTS AND CONCLUSION

Circ_0021087 and FOSB were lowly expressed in GC, whereas miR-184 had an opposite result. Circ_0021087 overexpression repressed GC cell proliferation and epithelial-mesenchymal transition (EMT) in xenograft models in vivo and induced GC cell apoptosis, repressed GC cell proliferation, EMT, migration and invasion in vitro. Circ_0021087 could elevate FOSB expression by adsorbing miR-184. MiR-184 mimic reversed the inhibitory influence of circ_0021087 overexpression on GC cell malignancy. Also, FOSB knockdown offset the suppressive impact of miR-184 silencing on GC cell malignancy. In conclusion, circ_0021087 played a repressive influence on GC progression by elevating FOSB expression by adsorbing miR-184, offering a new mechanism for circ_0021087 to inhibit the progression of GC.

摘要

背景

胃癌（GC）在全球癌症相关死亡原因中排名第三。环状 RNA hsa_circ_0021087（circ_0021087）在 GC 中发挥抑制作用。然而，circ_0021087 限制 GC 进展的机制尚不清楚。

材料和方法

通过实时定量聚合酶链反应（RT-qPCR）评估 circ_0021087、microRNA（miR）-184 和 FBJ 鼠骨肉瘤病毒癌基因同源物 B（FOSB）mRNA 的表达模式。进行了增益功能实验，以验证 circ_0021087 在体外和体内的生物学功能，包括细胞计数试剂盒-8（CCK-8）、5-乙炔基-2'-脱氧尿苷（EdU）、流式细胞术、transwell 和异种移植测定。通过 Western blot 和免疫组织化学（IHC）分析蛋白水平。通过生物信息学分析、双荧光素酶报告基因和 RNA 免疫沉淀（RIP）测定分析 circ_0021087 的调节机制。

结果与结论

circ_0021087 和 FOSB 在 GC 中低表达，而 miR-184 则相反。circ_0021087 过表达抑制体内异种移植模型中 GC 细胞的增殖和上皮-间充质转化（EMT），并诱导 GC 细胞凋亡，抑制 GC 细胞增殖、EMT、迁移和侵袭。circ_0021087 通过吸附 miR-184 可上调 FOSB 表达。miR-184 模拟逆转了 circ_0021087 过表达对 GC 细胞恶性的抑制作用。此外，FOSB 敲低抵消了 miR-184 沉默对 GC 细胞恶性的抑制作用。总之，circ_0021087 通过吸附 miR-184 上调 FOSB 表达对 GC 进展产生抑制作用，为 circ_0021087 抑制 GC 进展提供了新的机制。