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

作者：Xiaoning Wang, Xing Qin, Ming Yan, Jianbo Shi, Qin Xu, Zhihui Li, Wenjun Yang, Jianjun Zhang, Wantao Chen · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2019 · DOI：10.1186/s13046-019-1144-9 · 被引用次数：101 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、Cancer Cells and Metastasis

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 a...