异丙酚诱导的 miR-493-3p 通过抑制 DKK1 介导的 Wnt/-Catenin 信号激活抑制胃癌的生长和侵袭。

Propofol-Induced miR-493-3p Inhibits Growth and Invasion of Gastric Cancer through Suppression of DKK1-Mediated Wnt/-Catenin Signaling Activation.

机构信息

Department of Anesthesiology, The Third Affiliated Hospital of Shandong First Medical University, Jinan, 250031 Shandong, China.

Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Shandong First Medical University, Jinan, 250031 Shandong, China.

出版信息

Dis Markers. 2023 Jan 31;2023:7698706. doi: 10.1155/2023/7698706. eCollection 2023.

DOI:10.1155/2023/7698706

PMID:36762306

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9904924/

Abstract

PURPOSE

Gastric cancer (GC) is one of the most common malignant tumors and also one of the most deadly tumors. In recent years, studies have shown that propofol can inhibit the proliferation and metastasis of many tumor cells. In the present study, we aimed to investigate the underlying mechanism of propofol inhibition of the growth and invasion of GC cells.

METHODS

Human gastric cancer cell line SGC-7901 and human normal gastric epithelial cell GES-1 were cultured in high-glucose Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal bovine serum at 37°C with 5% CO. Propofol of different concentrations (0, 2, 5, and 10 g/mL) was used to treat SGC-7901, and miR-493-3p inhibitor was transfected into SGC-7901. The cell proliferation of SGC-7901 was analyzed by MTT as well as colony formation assay. The qRT-PCR was used to assess the expression of mRNA for key genes. We examined the protein expression of DKK1 and relative markers with western blot. Putative binding places of miR-493-3p on the 3'-untranslated area of DKK1 were predicted using bioinformatics and dual-luciferase method.

RESULTS

Propofol prohibited phenotypic features of GC, according to our findings. Furthermore, research into the underlying mechanisms of propofol's suppressive effects in GC cell proved that propofol therapy improved the degrees of expression of the potential tumor suppressor miR-493-3p. The inhibiting properties of propofol on GC cell development, migration, and invasion were abolished when propofol-induced miR493-3p was silenced with anti-miR-493-3p. We also found that this drug reversed epithelial-mesenchymal transformation in SGC-7901 cells via inducing miR-493-3p. Propofol-induced miR-493-3p decreases GC cell development via targeting DKK1 and hence inhibits Wnt/-catenin signaling, according to these findings.

CONCLUSION

Propofol-induced miR-493-3p decreased GC cell development via targeting DKK1 and hence inhibited Wnt/-catenin signaling, according to these findings.

摘要

目的

胃癌（GC）是最常见的恶性肿瘤之一，也是最致命的肿瘤之一。近年来的研究表明，丙泊酚可以抑制多种肿瘤细胞的增殖和转移。本研究旨在探讨丙泊酚抑制 GC 细胞生长和侵袭的潜在机制。

方法

将人胃癌细胞系 SGC-7901 和人正常胃上皮细胞 GES-1 在高糖 DMEM 中培养，其中含有 10%胎牛血清，在 37°C 和 5% CO 下培养。用不同浓度（0、2、5 和 10μg/ml）的丙泊酚处理 SGC-7901，并用 miR-493-3p 抑制剂转染 SGC-7901。用 MTT 法和集落形成实验分析 SGC-7901 的细胞增殖。用 qRT-PCR 评估关键基因的 mRNA 表达。用 Western blot 检测 DKK1 及相关标志物的蛋白表达。利用生物信息学和双荧光素酶法预测 miR-493-3p 在 DKK1 3'-UTR 上的潜在结合位点。

结果

根据我们的研究结果，丙泊酚抑制了 GC 的表型特征。此外，对丙泊酚抑制 GC 细胞作用机制的研究表明，丙泊酚治疗可提高潜在肿瘤抑制因子 miR-493-3p 的表达程度。用抗 miR-493-3p 沉默丙泊酚诱导的 miR493-3p 后，丙泊酚对 GC 细胞生长、迁移和侵袭的抑制作用被消除。我们还发现，这种药物通过诱导 miR-493-3p 使 SGC-7901 细胞发生上皮-间充质转化。丙泊酚诱导的 miR-493-3p 通过靶向 DKK1 降低 GC 细胞的发育，从而抑制 Wnt/-catenin 信号通路，根据这些发现。