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人脐带间充质干细胞来源的外泌体 miR-214-3p 通过调控 ACLY/GLUT1 调节胆囊癌的进展。

Human umbilical cord mesenchymal stem cell-derived exosomal miR-214-3p regulates the progression of gallbladder cancer by regulating ACLY/GLUT1.

机构信息

Department of General Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.

Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.

出版信息

Adv Clin Exp Med. 2024 May;33(5):499-510. doi: 10.17219/acem/169976.

DOI:10.17219/acem/169976
PMID:37747441
Abstract

BACKGROUND

Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes have been reported to be effective in the treatment of cancer. The miR-214-3p is a suppressor miRNA that has been extensively studied and has been proposed as a diagnostic and prognostic biomarker in some cancers.

OBJECTIVES

The aim of this study was to investigate whether the regulatory mechanism of hucMSC-derived exosomal miR-214-3p with GLUT1 and ACLY affects the proliferation and apoptosis of gallbladder cancer (GBC) cells.

MATERIAL AND METHODS

We found that the target genes of miR-214-3p on the TargetScan website contain GLUT1 and ACLY, and the targeting relationship was verified using luciferases. The GBC-SD cells overexpressing GLUT1 and ACLY were constructed to determine proliferation, apoptosis, migration, and other cellular activities.

RESULTS

We identified hucMSCs and exosomes, and found that the exosomes contained miR-214-3p. Furthermore, TargetScan predicted that miR-214-3p had base interactions with ACLY. Dual luciferase assays showed that miR-214-3p could inhibit ACLY (p < 0.05). The results of quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot showed that exosomal miR-214-3p could inhibit the expression of ACLY and GLUT1 (p < 0.05). Exosomal miR-214-3p can inhibit the proliferation, cloning and migration of GBC-SD cells (p < 0.05). The apoptosis of GBC-SD cells was increased (p < 0.05). The GBC-SD cells overexpressing ACLY and GLUT1 could reverse the efficacy of miR-214-3p.

CONCLUSIONS

Exosomal miR-214-3p can inhibit the downstream expression of ACLY and GLUT1. The ACLY and GLUT1 could affect the proliferation and apoptosis of GBC-SD cells.

摘要

背景

人脐带间充质干细胞(hucMSC)衍生的外泌体已被报道在癌症治疗中有效。miR-214-3p 是一种抑制性 miRNA,已被广泛研究,并被提议作为一些癌症的诊断和预后生物标志物。

目的

本研究旨在探讨 hucMSC 衍生的外泌体 miR-214-3p 是否通过 GLUT1 和 ACLY 调节影响胆囊癌细胞(GBC)的增殖和凋亡。

材料和方法

我们在 TargetScan 网站上发现 miR-214-3p 的靶基因包含 GLUT1 和 ACLY,并通过荧光素酶验证了靶向关系。构建了过表达 GLUT1 和 ACLY 的 GBC-SD 细胞,以确定增殖、凋亡、迁移等细胞活性。

结果

我们鉴定了 hucMSCs 和外泌体,并发现外泌体含有 miR-214-3p。此外,TargetScan 预测 miR-214-3p 与 ACLY 有碱基相互作用。双荧光素酶报告基因实验显示,miR-214-3p 可抑制 ACLY(p<0.05)。实时定量聚合酶链反应(RT-qPCR)和 Western blot 结果显示,外泌体 miR-214-3p 可抑制 ACLY 和 GLUT1 的表达(p<0.05)。外泌体 miR-214-3p 可抑制 GBC-SD 细胞的增殖、克隆和迁移(p<0.05)。GBC-SD 细胞的凋亡增加(p<0.05)。过表达 ACLY 和 GLUT1 的 GBC-SD 细胞可逆转 miR-214-3p 的疗效。

结论

外泌体 miR-214-3p 可抑制 ACLY 和 GLUT1 的下游表达。ACLY 和 GLUT1 可影响 GBC-SD 细胞的增殖和凋亡。

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