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Circ_0110805敲低通过miR-299-3p/ENDOPDI轴增强顺铂敏感性并抑制胃癌进展。

Circ_0110805 Knockdown Enhances Cisplatin Sensitivity and Inhibits Gastric Cancer Progression by miR-299-3p/ENDOPDI Axis.

作者信息

Yang Xi, Zhang Qunxiong, Guan Bugao

机构信息

Digestive Department, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou, Jiangsu, People's Republic of China.

Department of General Surgery, People's Hospital of Jinhu, Huaian, Jiangsu, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Nov 6;13:11445-11457. doi: 10.2147/OTT.S279563. eCollection 2020.

DOI:10.2147/OTT.S279563
PMID:33192077
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7654533/
Abstract

BACKGROUND

Gastric cancer is a prevalent primary stomach tumor. Cisplatin is frequently used to treat gastric cancer. However, the resistance of cisplatin in gastric cancer often occurs, which brings a heavy burden to gastric cancer treatment.

METHODS

In this study, we revealed a novel underlying mechanism about cisplatin-resistant effect in gastric cancer. A Cell Counting Kit-8 (CCK-8) cell viability assay and a xenograft model were performed to evaluate the function of circRNA in the cisplatin resistance of gastric cancer.

RESULTS

Compared with control groups, we observed that circ_0110805 was highly expressed, the mRNA and protein expression levels of ENDOPDI were dramatically upregulated, and the expression of miR-299-3p was significantly downregulated in gastric cancer cells, cisplatin-resistant gastric cancer tissues or cells. Functionally, circ_0110805 knockdown improved cisplatin sensitivity, induced cell apoptosis, whereas repressed cell viability, migration and invasion in AGS/DDP and HGC-27/DDP cells, which was reversed by miR-299-3p inhibitor. Additionally, ENDOPDI overexpression hindered the effects of miR-299-3p on cisplatin sensitivity and gastric cancer progression. Circ_0110805 knockdown enhanced cisplatin sensitivity in vivo. Mechanistically, circ_0110805 acted as a sponge of miR-299-3p and its targeted ENDOPDI.

CONCLUSION

We showed that circ_0110805 knockdown increased the sensitivity of gastric cancer to cisplatin, which also repressed gastric cancer progression by sponging miR-299-3p to downregulate ENDOPDI expression. It might provide a new insight for future studying cisplatin-resistant gastric cancer.

摘要

背景

胃癌是一种常见的原发性胃部肿瘤。顺铂常用于治疗胃癌。然而，胃癌中顺铂耐药经常发生，这给胃癌治疗带来了沉重负担。

方法

在本研究中，我们揭示了一种关于胃癌顺铂耐药作用的新潜在机制。进行细胞计数试剂盒-8（CCK-8）细胞活力测定和异种移植模型以评估环状RNA在胃癌顺铂耐药中的作用。

结果

与对照组相比，我们观察到在胃癌细胞、顺铂耐药胃癌组织或细胞中，circ_0110805高表达，ENDOPDI的mRNA和蛋白表达水平显著上调，而miR-299-3p的表达显著下调。在功能上，circ_0110805敲低提高了顺铂敏感性，诱导细胞凋亡，同时抑制了AGS/DDP和HGC-27/DDP细胞的活力、迁移和侵袭，而miR-299-3p抑制剂可逆转这些作用。此外，ENDOPDI过表达阻碍了miR-299-3p对顺铂敏感性和胃癌进展的影响。circ_0110805敲低在体内增强了顺铂敏感性。机制上，circ_0110805作为miR-299-3p及其靶向的ENDOPDI的海绵。

结论

我们表明，circ_0110805敲低增加了胃癌对顺铂的敏感性，同时通过海绵吸附miR-299-3p下调ENDOPDI表达来抑制胃癌进展。这可能为未来研究顺铂耐药胃癌提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1093/7654533/5b7d4ef52e3c/OTT-13-11445-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1093/7654533/5b7d4ef52e3c/OTT-13-11445-g0008.jpg

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