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Loss of exosomal miR-3188 in cancer-associated fibroblasts contributes to HNC progression.

Abstract：

BACKGROUND:Head and neck cancer (HNC) is one of the most common deadly diseases worldwide. An increasing number of studies have recently focused on the malignant functions of cancer-associated fibroblasts (CAFs) in numerous cancers. However, the underlying mechanisms by which CAF-derived exosomes promote tumor progression need to be further elucidated. This study aims to determine whether the loss of specific miRNAs in CAF-derived exosomes may be involved in the malignant transformation of HNC. METHODS:MiRNA array and real-time PCR assays were used to analyze the differential expression of miRNAs in exosomes from normal fibroblasts (NFs) and CAFs. Cell proliferation, EdU incorporation, colony formation, apoptosis, cell cycle distribution and xenograft assays were performed to examine the effects of miR-3188 on HNC in vitro and in vivo. Real-time PCR, western blotting and luciferase reporter assays were used to identify the target genes of miR-3188. Furthermore, tumor-bearing mouse models were used to prove the potential therapeutic value of miR-3188-loaded exosomes in HNC. RESULTS:Our results showed that miR-3188 expression is reduced in exosomes and their parental CAFs from HNC tissues. In addition, miR-3188 can be transferred from fibroblasts to HNC cells by exosomes. Further exploration demonstrated that exosomal miR-3188 can influence the proliferation and apoptosis of HNC cells by directly targeting B-cell lymphoma 2 (BCL2) in vitro and in vivo. More importantly, we also found that miR-3188-loaded exosomes significantly inhibited tumor growth in vivo. CONCLUSIONS:Our findings revealed that CAF-derived exosomes contain lower miR-3188 levels than NFs, and the loss of miR-3188 in exosomes contributes to the malignant phenotypes of HNC cells through the derepression of BCL2. Furthermore, these data suggest the potential therapeutic value of exosomal miR-3188 for inhibiting HNC growth.

journal_name

J Exp Clin Cancer Res

journal_title

Journal of experimental & clinical cancer research : CR

authors

Wang X,Qin X,Yan M,Shi J,Xu Q,Li Z,Yang W,Zhang J,Chen W

doi

10.1186/s13046-019-1144-9

subject

Has Abstract

pub_date

2019-04-08 00:00:00

pages

151

issue

eissn

0392-9078

issn

1756-9966

pii

10.1186/s13046-019-1144-9

journal_volume

pub_type

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Loss of exosomal miR-3188 in cancer-associated fibroblasts contributes to HNC progression.