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miR-221-5p对胃癌细胞顺铂敏感性的促进作用及其通过调控DDR1对细胞增殖和凋亡的影响

Promotion of miR-221-5p on the Sensitivity of Gastric Cancer Cells to Cisplatin and Its Effects on Cell Proliferation and Apoptosis by Regulating DDR1.

作者信息

Jiang Xiaomeng, Jiang Menglin, Guo Shuhua, Cai Pengpeng, Wang Wei, Li Yi

机构信息

Department of Digestive, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, 211166, People's Republic of China.

Biomedical Sciences Department, University of Tennessee Health Sciences Center, Memphis, TN 38105, USA.

出版信息

Onco Targets Ther. 2020 Mar 18;13:2333-2345. doi: 10.2147/OTT.S232953. eCollection 2020.

Abstract

PURPOSE

This research aimed to explore the role of miR-221-5p on the sensitivity of gastric cancer cells to cisplatin, and the proliferation and invasion of gastric cancer cells by regulating DDR1.

PATIENTS AND METHODS

Altogether 69 patients who treated with radical gastrectomy from January 2014 to January 2016 were collected. With the agree of the patients, 69 gastric carcinoma and 69 adjacent tissues were taken, respectively, during the operation, and gastric carcinoma and human gastric mucosa cells were purchased. RT-PCR was used for detection of the expression level of miR-221-5p and DDR1. Wound healing assay and CCK-8 assay were used for exploration of the cell migration and viability. Western blot and double luciferase reporter gene were performed to determine the target gene of miR-221-5p.

RESULTS

It was showed that miR-221-5p expression was decreased in GC tissues and cell lines. The high expression of miR-221-5p reduced the resistance of GC cells to cisplatin and inhibited the proliferation and migration of gastric cancer cells. The high expression of miR-221-5p promoted the proliferation, invasion and migration of GC cells. In addition, we found that DDR1 was a direct target gene of miR-221-5p in GC cells. We found that DDR1 expression increased in gastric carcinoma. Moreover, there was a negative correlation of DDR1 with the expression level of miR-221-5p. The increase of miR-221-5p increased the chemosensitivity of GC cells to cisplatin, and inhibited the proliferation, invasion, migration and EMT of GC cells by targeting DDR1.

CONCLUSION

The above research indicated that miR-221-5p may be a target for enhancing cisplatin chemotherapy sensitivity in gastric cancer patients.

摘要

目的

本研究旨在探讨miR-221-5p通过调控盘状结构域受体1(DDR1)对胃癌细胞顺铂敏感性以及胃癌细胞增殖和侵袭的作用。

患者与方法

收集2014年1月至2016年1月期间接受根治性胃切除术的69例患者。经患者同意,术中分别获取69例胃癌组织及69例癌旁组织,并购买胃癌及人胃黏膜细胞。采用逆转录-聚合酶链反应(RT-PCR)检测miR-221-5p和DDR1的表达水平。采用伤口愈合试验和细胞计数试剂盒-8(CCK-8)试验探究细胞迁移和活力。进行蛋白质免疫印迹法(Western blot)和双荧光素酶报告基因检测以确定miR-221-5p的靶基因。

结果

结果显示,miR-221-5p在胃癌组织和细胞系中表达降低。miR-221-5p的高表达降低了胃癌细胞对顺铂的耐药性,并抑制了胃癌细胞的增殖和迁移。DDR1的高表达促进了胃癌细胞的增殖、侵袭和迁移。此外,我们发现DDR1是胃癌细胞中miR-221-5p的直接靶基因。我们发现DDR1在胃癌中表达增加。而且,DDR1与miR-221-5p的表达水平呈负相关。miR-221-5p的增加提高了胃癌细胞对顺铂的化疗敏感性,并通过靶向DDR1抑制了胃癌细胞的增殖、侵袭、迁移和上皮-间质转化(EMT)。

结论

上述研究表明,miR-221-5p可能是提高胃癌患者顺铂化疗敏感性的一个靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d20/7090206/296cb5fd04f7/OTT-13-2333-g0001.jpg

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