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微小 RNA-24 通过靶向 DND1 抑制人胃癌的增殖、迁移和侵袭并增强化疗敏感性。

MicroRNA-24 inhibits the proliferation, migration and invasion and enhances chemosensitivity of human gastric cancer by targeting DND1.

机构信息

Department of General Surgery, Tianjin First Central Hospital, tianjin 300192, China.

出版信息

J BUON. 2020 Mar-Apr;25(2):1001-1006.

PMID:32521898
Abstract

PURPOSE

Gastric cancer causes significant human mortality and is the fourth prevalent type of cancer across the globe. The gastric cancer treatment is hurdled by late diagnosis due to unavailability of biomarkers, lack of potent therapeutic targets and adverse effects of chemotherapy. Recent reports have indicated that miR-24 acts a tumor suppressor in different cancers. This study explored the role and therapeutic implications of miR-24 in gastric cancer.

METHODS

Expression analysis was carried out in gastric cancer tissues and cell lines by qRT-PCR. Proliferation rate was monitored by WST-1 assay. Transwell assay was used to determine cell invasion and wound healing assay was used for cell migration. Protein expression analysis was carried out by western blot analysis.

RESULTS

The results showed that miR-24 was significantly suppressed in gastric cancer tissues and cell lines. Overexpression of miR-24 in SNU-1 gastric cancer cells resulted in decline of proliferation rate in a time-dependent manner. In silico analysis together with the dual luciferase assay revealed RNA binding protein DND1 to be the target of miR-24. Expression analysis of DND1 was found to be significantly overexpressed in gastric cancer tissues and cell lines. Suppression of DND1 suppressed the proliferation of gastric cancer cells. Wound healing and transwell assay revealed that miR-24 overexpression also inhibited the migration and invasion and also enhanced the chemosensitivity of the SNU1 gastric cancer cells.

CONCLUSION

Taken together, miR-24 may prove to be an important therapeutic target for the treatment of gastric cancer and warrants further studies.

摘要

目的

胃癌导致了大量的人类死亡,是全球第四大常见癌症。由于缺乏生物标志物、缺乏有效的治疗靶点和化疗的副作用,胃癌的治疗受到了阻碍。最近的报告表明,miR-24 在不同的癌症中充当肿瘤抑制因子。本研究探讨了 miR-24 在胃癌中的作用和治疗意义。

方法

通过 qRT-PCR 在胃癌组织和细胞系中进行表达分析。通过 WST-1 测定法监测增殖率。通过 Transwell 测定法测定细胞侵袭,通过划痕愈合测定法测定细胞迁移。通过 Western blot 分析进行蛋白表达分析。

结果

结果表明,miR-24 在胃癌组织和细胞系中显著受抑制。在 SNU-1 胃癌细胞中过表达 miR-24 导致增殖率呈时间依赖性下降。计算机分析和双荧光素酶测定显示,RNA 结合蛋白 DND1 是 miR-24 的靶标。在胃癌组织和细胞系中发现 DND1 的表达明显过表达。抑制 DND1 的表达抑制了胃癌细胞的增殖。划痕愈合和 Transwell 测定表明,miR-24 的过表达也抑制了 SNU1 胃癌细胞的迁移和侵袭,并增强了它们的化疗敏感性。

结论

综上所述,miR-24 可能成为治疗胃癌的重要治疗靶点,值得进一步研究。

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