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精准热疗诱导的 miRNA-409-3p 上调通过靶向 KLF17 抑制胃癌细胞的迁移、侵袭和 EMT。

Precision hyperthermia-induced miRNA-409-3p upregulation inhibits migration, invasion, and EMT of gastric cancer cells by targeting KLF17.

机构信息

Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.

Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, PR China.

出版信息

Biochem Biophys Res Commun. 2021 Apr 16;549:113-119. doi: 10.1016/j.bbrc.2021.02.063. Epub 2021 Mar 2.

Abstract

Hyperthermic intraperitoneal chemotherapy (HIPEC) is widely used for clinical treatment of advanced cancers. However, the regulatory mechanism underlying precise hyperthermia treatment in advanced gastric cancer (AGC) remains unclear. MiR-409-3p is reportedly downregulated in a variety of cancers, although its role in regulating treatment of AGC by precise hyperthermia remains unclear. The underlying mechanisms of miRNA-medicated regulation have been investigated using predicted and validated miRNA-gene targets, confirming the role of miRNA in HIPEC; METHODS: We used quantitative real time PCR (qRT-PCR) to detect miR-409-3p expression in gastric cancer (GC), as well as adjacent normal tissues, following exposure to varying temperatures. We detected miR-409-3p targets using dual-luciferase assay, then performed cell apoptosis, western blotting, invasion, and migration assays to detect GC functions; RESULTS: MiR-409-3p was upregulated and downregulated in precise hyperthermia and AGC, respectively. Moreover, miR-409-3p upregulated the Krüppel-like-factor 17 (KLF17), which subsequently inhibited migration, invasiveness, and epithelial-mesenchymal transition (EMT) but promoted apoptosis in GC cells; CONCLUSIONS: Precise hyperthermia upregulated miR-409-3p and KLF17 indirectly, thereby inhibiting invasion, migration, and EMT, and promoting apoptosis of gastric cancer cells.

摘要

腹腔内热化疗(HIPEC)广泛用于晚期癌症的临床治疗。然而,精确高温治疗晚期胃癌(AGC)的确切调节机制仍不清楚。据报道,miR-409-3p 在多种癌症中下调,尽管其在调节精确高温治疗 AGC 中的作用尚不清楚。已经使用预测和验证的 miRNA-基因靶标研究了 miRNA 介导的调节的潜在机制,证实了 miRNA 在 HIPEC 中的作用;方法:我们使用定量实时 PCR(qRT-PCR)检测暴露于不同温度后胃癌(GC)以及相邻正常组织中 miR-409-3p 的表达。我们使用双荧光素酶测定法检测 miR-409-3p 靶标,然后进行细胞凋亡、Western blot、侵袭和迁移测定以检测 GC 功能;结果:miR-409-3p 在精确高温和 AGC 中分别上调和下调。此外,miR-409-3p 上调了 Krüppel 样因子 17(KLF17),随后抑制了 GC 细胞的迁移、侵袭和上皮-间充质转化(EMT),但促进了细胞凋亡;结论:精确高温间接上调 miR-409-3p 和 KLF17,从而抑制胃癌细胞的侵袭、迁移和 EMT,并促进其凋亡。

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