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来自血小板源性生长因子-BB诱导的癌相关成纤维细胞衍生外泌体的MiR-3529-3p促进口腔鳞状细胞癌的恶性进展。

MiR-3529-3p from PDGF-BB-induced cancer-associated fibroblast-derived exosomes promotes the malignancy of oral squamous cell carcinoma.

作者信息

You Dingyun, Wang Yanghao, Xu Jianguo, Yang Rongqiang, Wang Weizhou, Wang Xiaofang, Cao Xue, Li Yiting, Yu Lifu, Wang Weihong, Shi Yanan, Zhang Changbin, Yang Hefeng, He Yongwen, Bian Li

机构信息

Department of Dental Research, The Affiliated Stomatological Hospital of Kunming Medical University, Kunming, 650106, Yunnan, China.

The Yunnan Key Laboratory of Stomatological, Kunming Medical University, Kunming, 650106, Yunnan, China.

出版信息

Discov Oncol. 2023 Sep 5;14(1):166. doi: 10.1007/s12672-023-00753-9.

Abstract

AIMS

This study aims to explore the role of exosomes from cancer-associated fibroblasts (CAFs) induced by PDGF-BB in promoting the malignancy of oral squamous cell carcinoma (OSCC) and provide new insight into the mechanism of OSCC progression and its treatment.

MAIN METHODS

Exosomes were extracted from human oral mucosa fibroblasts (hOMFs) and CAFs. Differentially expressed miRNAs of exosomes between hOMFs and CAFs were analysed using high-throughput sequencing and self-programmed R software. Cal-27, a human tongue squamous carcinoma cell line, was treated with exosomes. Differentially expressed miRNAs between clinical cancer tissues and adjacent tissues and between hOMF and CAF exosomes were verified by qRT‒PCR. The effect of miR-3529-3p on Cal-27 cells was clarified by overexpressing or knocking down miR-3529-3p in Cal-27 cells. Sample expression and differentially expressed miRNA expression were compared between cancer and paracarcinoma tissues.

KEY FINDINGS

We found that exosomes from CAFs (CAF-Exos) were internalized by tongue squamous carcinoma cells and promoted their proliferation, migration, invasion, and antiapoptotic effects. MiR-3529-3p was a significant differentially expressed miRNA between CAF-Exos and exosomes from hOMFs (hOMF-Exos). The overexpression of miR-3529-3p promoted proliferation, migration, and invasion and inhibited apoptosis of Cal-27 cells.

SIGNIFICANCE

This study explores the role of PDGF-BB-induced CAFs in promoting malignancy in OSCC. This study will provide new insight into the mechanism of OSCC progression and its treatment.

摘要

目的

本研究旨在探讨血小板源性生长因子-BB(PDGF-BB)诱导的癌症相关成纤维细胞(CAFs)外泌体在促进口腔鳞状细胞癌(OSCC)恶性进展中的作用,并为OSCC进展机制及其治疗提供新的见解。

主要方法

从人口腔黏膜成纤维细胞(hOMFs)和CAFs中提取外泌体。使用高通量测序和自编R软件分析hOMFs和CAFs外泌体中差异表达的微小RNA(miRNAs)。用外泌体处理人舌鳞状癌细胞系Cal-27。通过qRT-PCR验证临床癌组织与癌旁组织之间以及hOMF和CAF外泌体之间差异表达的miRNAs。通过在Cal-27细胞中过表达或敲低miR-3529-3p来阐明其对Cal-27细胞的影响。比较癌组织和癌旁组织之间的样本表达及差异表达的miRNA表达。

主要发现

我们发现CAFs来源的外泌体(CAF-Exos)被舌鳞状癌细胞内化,并促进其增殖、迁移、侵袭和抗凋亡作用。miR-3529-3p是CAF-Exos与hOMFs来源的外泌体(hOMF-Exos)之间显著差异表达的miRNA。miR-3529-3p的过表达促进了Cal-27细胞的增殖、迁移和侵袭,并抑制了其凋亡。

意义

本研究探讨了PDGF-BB诱导的CAFs在促进OSCC恶性进展中的作用。本研究将为OSCC进展机制及其治疗提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ae/10480386/a3ff9b23d2e6/12672_2023_753_Fig1_HTML.jpg

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