类有机物
小RNA
微泡
结直肠癌
下调和上调
癌症研究
生物
细胞生长
外体
细胞培养
细胞生物学
癌症
基因
遗传学
作者
Hiroshi Nagai,Masatake Kuroha,Tomoyuki Handa,Hideaki Karasawa,Shinobu Ohnuma,Takeo Naito,Rintaro Moroi,Yoshitake Kanazawa,Hisashi Shiga,Shin Hamada,Yoichi Kakuta,Takeshi Naitoh,Yoshitaka Kinouchi,Tooru Shimosegawa,Atsushi Masamune
出处
期刊:Digestion
[S. Karger AG]
日期:2021-01-01
卷期号:102 (6): 860-869
被引量:10
摘要
<b><i>Introduction:</i></b> Exosomes are membrane-enclosed nanovesicles, which are increasingly being recognized as important cell communication components for their role in transmitting microRNAs (miRNAs). No previous study has addressed the exosomal miRNA profile in colorectal adenomas (CRAs) because the long-term culture of CRA is challenging. This study aimed to identify the miRNA signature in organoid exosomes derived from human CRA and colorectal cancer (CRC) samples. <b><i>Methods:</i></b> Organoid cultures were developed from resected colorectal tissues of patients with CRA or CRC undergoing surgery or endoscopic mucosal resection. Exosomes were prepared from the conditioned medium of the organoids. miRNAs were prepared from the exosomes and their source organoids. The miRNA expression profiles were compared using microarray analysis. The impact of alteration of miRNA expression on cell proliferation was examined using miRNA mimics or inhibitors in HT-29 human CRC cells. <b><i>Results:</i></b> We established 6 organoid lines from CRC and 8 organoid lines from CRA. Exosomal miRNA signatures were different between the organoids derived from CRA and CRC. Both exosomal and cellular miR-1246 expressions were upregulated in CRC-derived organoids compared to their expression in CRA-derived organoids. Alteration of miR-1246 expression by the miR-1246 mimic or inhibitor increased or decreased cell proliferation in HT-29 cells, respectively. <b><i>Conclusions:</i></b> We report for the first time the miRNA profiles of exosomes in CRA- and CRC-derived organoids. The upregulation of miR-1246 might play a role in increased cell proliferation in the process of CRA-carcinoma transition.
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