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长链非编码RNA TPTEP1通过miR-548d-3p/KLF9/PER1轴抑制胃癌细胞的迁移和侵袭。

LncRNA TPTEP1 inhibits the migration and invasion of gastric cancer cells through miR-548d-3p/KLF9/PER1 axis.

作者信息

Huang You, Wang Jun, Zhang Hangsheng, Xiang Yuan, Dai Zhoutong, Zhang Huimin, Li Jiapeng, Li Hui, Liao Xinghua

机构信息

Institute of Biology and Medicine, Wuhan University of Science and Technology, 430000, PR China.

Department of Medical Laboratory, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Hubei 430014, PR China.

出版信息

Pathol Res Pract. 2022 Sep;237:154054. doi: 10.1016/j.prp.2022.154054. Epub 2022 Jul 30.

Abstract

BACKGROUND

Despite the development of many methods and new therapeutic agents, the survival and prognosis of patients with gastric cancer are still poor. The role of TPTEP1 in gastric cancer has not been reported.

METHODS

Wound healing assay and transwell assay analysis TPTEP1/miR-548d-3p/KLF9/PER1 effect on migration and invasiveness of gastric cells. Western blot and RT-qPCR certificate TPTEP1/miR-548d-3p/KLF9/PER1transcription and expression of migration and invasion related genes. Luciferase assay was used to determine the adsorption of miR-548d-3p by TPTEP1 sponge, the targeting of miR-548d-3p to KLF9, and the binding of KLF9 to the promoter of PER1. immunohistochemical assay and H&E staining prove the function of TPTEP1 and miR-548d-3p in nude mice model of gastric cancer.

RESULTS

TPTEP1 inhibited its expression by sponge adsorption of miR-548d-3p. miR-548d-3p targets KLF9 3'UTR to inhibit its expression, and KLF9 binds to the PER1 promoter to promote its expression.TPTEP1/KLF9/PER1 inhibits gastric cancer cell migration and invasion, and miR-548d-3p does the opposite.

CONCLUSIONS

Our data suggest that TPTEP1 affects gastric cancer progression by regulating the miR-548d-3p/KLF9/PER1 axis. Targeting this pathway may provide new therapeutic opportunities for gastric cancer.

摘要

背景

尽管已开发出多种方法和新型治疗药物,但胃癌患者的生存率和预后仍然很差。TPTEP1在胃癌中的作用尚未见报道。

方法

采用伤口愈合试验和Transwell试验分析TPTEP1/miR-548d-3p/KLF9/PER1对胃细胞迁移和侵袭的影响。蛋白质免疫印迹法和逆转录-定量聚合酶链反应验证TPTEP1/miR-548d-3p/KLF9/PER1对迁移和侵袭相关基因的转录和表达。荧光素酶报告基因检测用于确定TPTEP1海绵对miR-548d-3p的吸附、miR-548d-3p对KLF9的靶向作用以及KLF9与PER1启动子的结合。免疫组织化学检测和苏木精-伊红染色在胃癌裸鼠模型中证实TPTEP1和miR-548d-3p的功能。

结果

TPTEP1通过海绵吸附miR-548d-3p抑制其表达。miR-548d-3p靶向KLF9的3'非翻译区抑制其表达,而KLF9与PER1启动子结合促进其表达。TPTEP1/KLF9/PER1抑制胃癌细胞的迁移和侵袭,而miR-548d-3p则相反。

结论

我们的数据表明,TPTEP1通过调节miR-548d-3p/KLF9/PER1轴影响胃癌进展。靶向该途径可能为胃癌提供新的治疗机会。

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