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癌症相关成纤维细胞中外泌体miR-34c-5p的缺失对维持喉癌细胞的干细胞样表型至关重要。

Loss of exosomal miR-34c-5p in cancer-associated fibroblast for the maintenance of stem-like phenotypes of laryngeal cancer cells.

作者信息

Wang Mei, Zhuoma Ciwang, Liu Xiaojin, Huang Qiang, Cai Guoyu, Sang Ge, Zhou Liang, Du Huaidong, Wu Chunping

机构信息

Department of Otolaryngology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Department of Otolaryngology, Shigatse People's Hospital, Tibet, China.

出版信息

Head Neck. 2022 Nov;44(11):2437-2451. doi: 10.1002/hed.27155. Epub 2022 Jul 22.

Abstract

BACKGROUND

Cancer-associated fibroblasts (CAFs) reconstitute cancer stemness. This study aims to investigate whether the loss of CAF-derived exosomal miR-34c-5p contributes to the maintenance of stem-like properties of laryngeal squamous cell carcinoma (LSCC).

METHODS

Exosomes from primarily cultured CAFs and paired normal fibroblasts (NFs) were collected and identified. The differential expression of exosomal miR-34c-5p between CAFs and NFs was detected by next-generation sequencing. In vitro and in vivo assays were performed to examine the effects of miR-34c-5p on the maintenance of stem-like properties.

RESULTS

MiR-34c-5p expression is significantly reduced in CAF-derived exosomes. In vitro and in vivo assays revealed that exosomal miR-34c-5p can regulate the stem-like properties of LSCC cells, such as proliferation, invasion, sphere and plate colony formation, chemoresistance, tumorigenicity in nude mice, as well as the expression of cancer stem cell genes.

CONCLUSIONS

Loss of miR-34c-5p in CAF-derived exosomes contributes to the maintenance of stem-like phenotypes of LSCC.

摘要

背景

癌症相关成纤维细胞(CAFs)重塑癌症干性。本研究旨在探究CAF来源的外泌体miR-34c-5p缺失是否有助于维持喉鳞状细胞癌(LSCC)的干细胞样特性。

方法

收集并鉴定原代培养的CAFs和配对的正常成纤维细胞(NFs)来源的外泌体。通过下一代测序检测CAFs和NFs之间外泌体miR-34c-5p的差异表达。进行体外和体内实验以检测miR-34c-5p对维持干细胞样特性的影响。

结果

CAF来源的外泌体中miR-34c-5p表达显著降低。体外和体内实验表明,外泌体miR-34c-5p可调节LSCC细胞的干细胞样特性,如增殖、侵袭、球体和平板集落形成、化疗耐药性、裸鼠致瘤性以及癌症干细胞基因的表达。

结论

CAF来源的外泌体中miR-34c-5p缺失有助于维持LSCC的干细胞样表型。

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