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人脐带间充质干细胞来源的外泌体 microRNA-181a 通过介导 KDM5C 延缓鼻咽癌的发展。

Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-181a retards nasopharyngeal carcinoma development by mediating KDM5C.

机构信息

School of the Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410128, China.

Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.

出版信息

J Cancer Res Clin Oncol. 2021 Oct;147(10):2867-2877. doi: 10.1007/s00432-021-03684-6. Epub 2021 Jul 4.

Abstract

OBJECTIVE

It has been studied that mesenchymal stem cells (MSCs)-derived exosomes could suppress tumor growth in nasopharyngeal carcinoma (NPC) and microRNA-181a (miR-181a) could mediate drug resistance in NPC. Focused on this work, the mechanism of human umbilical cord MSCs (hUC-MSCs)-derived exosomal miR-181a was explored in NPC cell progression.

METHODS

NPC tissues and normal tissues were obtained from patients, and miR-181a and KDM5C expression was examined. hUC-MSCs-derived exosomes were extracted, identified and co-cultured with NPC cells (C666-1 and SUNE1). C666-1 cell progression in vitro and/or tumor growth in vivo were examined after incubation with exosomes, miR-181a or lysine-specific demethylase 5C (KDM5C). miR-181a and KDM5C expression were examined in NPC.

RESULTS

miR-181a expression was reduced while KDM5C expression was elevated in NPC. hUC-MSCs-derived exosomes restrained NPC cell growth in vivo and in vitro. Depleting or restoring exosomal miR-181a promoted or delayed NPC cell progression. KDM5C silencing suppressed NPC cell progression.

CONCLUSION

This study concluded that hUC-MSCs-derived exosomal miR-181a retards NPC development via negatively modulating KDM5C, serving as a candidate reference for the therapy of NPC.

摘要

目的

有研究表明间充质干细胞(MSC)衍生的外泌体可以抑制鼻咽癌(NPC)的肿瘤生长,微小 RNA-181a(miR-181a)可以介导 NPC 中的药物耐药性。本研究聚焦于此,探讨了人脐带 MSC(hUC-MSC)衍生的外泌体 miR-181a 在 NPC 细胞进展中的作用机制。

方法

从患者中获取 NPC 组织和正常组织,检测 miR-181a 和 KDM5C 的表达。提取、鉴定 hUC-MSC 衍生的外泌体,并与 NPC 细胞(C666-1 和 SUNE1)共培养。孵育外泌体、miR-181a 或赖氨酸特异性去甲基化酶 5C(KDM5C)后,检测 C666-1 细胞体外进展和/或体内肿瘤生长情况。检测 NPC 中 miR-181a 和 KDM5C 的表达。

结果

miR-181a 在 NPC 中表达降低,KDM5C 表达升高。hUC-MSC 衍生的外泌体抑制 NPC 细胞在体内和体外的生长。耗尽或恢复外泌体 miR-181a 促进或延缓 NPC 细胞进展。沉默 KDM5C 抑制 NPC 细胞进展。

结论

本研究表明,hUC-MSC 衍生的外泌体 miR-181a 通过负调控 KDM5C 抑制 NPC 的发展,可为 NPC 的治疗提供候选参考。

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