微泡
癌相关成纤维细胞
下调和上调
癌症研究
外体
结直肠癌
流式细胞术
肿瘤进展
癌症
肿瘤微环境
癌细胞
细胞生长
小RNA
生物
化学
医学
分子生物学
内科学
肿瘤细胞
生物化学
基因
遗传学
作者
Weikun Shi,Yuxin Liu,Xiaoyuan Qiu,Lu Yang,Guole Lin
出处
期刊:Carcinogenesis
[Oxford University Press]
日期:2023-04-01
卷期号:44 (4): 317-327
被引量:5
标识
DOI:10.1093/carcin/bgad014
摘要
Colorectal cancer (CRC) is the second leading cause of cancer-induced death in the world. Cancer-associated fibroblasts (CAFs) released exosomes that contributed to cancer progression. This research was carried out to study the influence of CRC-associated fibroblasts-derived exosomes on the phenotype of CRC cells and the underlying mechanism. CAFs-derived exosomes (CAFs-exo) and normal fibroblasts (NFs)-derived exosomes (NFs-exo) were recognized by transmission electronic microscopy, nanoparticle tracking analysis and western blot analysis. Cell counting kit-8, flow cytometry analysis, colony formation assay, Transwell, qRT-PCR, immunofluorescence, immunohistochemistry staining and xenografts model were carried out to proceed with function studies in vitro and in vivo. The results showed that CAFs-exo induced cell proliferation, migration and invasion, while NFs-exo did not influence the tumor biological properties of CRC cells. Using qRT-PCR, miR-345-5p was observed to be a notably up-regulated miRNA in CAFs-exo compared to NFs-exo. CAFs-exo could mediate the transfer of miR-345-5p to CRC cells, and downregulation of miR-345-5p in CAFs notably reversed the pro-tumoral effect of CAFs-exo on CRC cells. Based on online prediction database, CDKN1A was proved as a direct downstream target of miR-345-5p in CRC cells, which was lowly expressed and negatively associated with miR-345-5p in CRC tumors. Furthermore, miR-345-5p upregulation-mediated tumor biological behaviors were abrogated by exogenous CDKN1A. In CRC cells-beared tumor xenograft, CAFs-exo administration promoted tumor growth and decreased CDKN1A expression, whereas miR-345-5p inhibition reversed these effects. The present study revealed that by interacting with CDKN1A, CAF-derived exosomal miR-345-5p promotes CRC progression and metastasis.
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