Exosomal miR-200c-3p negatively regulates the migraion and invasion of lipopolysaccharide (LPS)-stimulated colorectal cancer (CRC)
Exosomal miR-200c-3p negatively regulates the migraion and invasion of lipopolysaccharide (LPS)-stimulated colorectal cancer (CRC)
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DOI：
10.1186/s12860-020-00291-0
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发表时间：
2020-06-29
影响因子：
2.8
通讯作者：
Zhao, Ren
中科院分区：
文献类型：
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作者：
Jiang, Yimei;Ji, Xiaopin;Zhao, Ren
结直肠癌（Colorectal cancer，CRC）是一种常见的恶性肿瘤，也是导致死亡的主要原因.脂多糖（LPS）是肠道微生物组中丰富的组分，可能通过调节CRC衍生的外泌体的miRNA组成参与CRC进展和转移。在这项研究中，我们的目的是鉴定外泌体中的miRNA种类，其在LPS刺激后调节CRC进展。结果第一，发现大肠癌细胞外泌体在LPS刺激后miRNA表达谱发生了变化。在差异表达的miRNAs中，我们鉴定了miR-200 c-3 p作为CRC进展和转移的潜在关键调节因子。回顾性分析显示，miR-200 c-3 p在CRC肿瘤组织中升高，但在CRC患者血清外泌体中降低。体外实验表明，外泌体miR-200 c-3 p表达不影响CRC细胞增殖，但在LPS存在下负调节其迁移和侵袭能力。外泌体中miR-200 c-3 p的水平影响外泌体中锌指E-box-binding homeobox-1（ZEB-1）mRNA的表达，并进一步改变CRC细胞中ZEB-1蛋白的表达。此外，外泌体miR-200 c-3 p促进HCT-116细胞的凋亡。结论外泌体miR-200 c-3 p抑制大肠癌的侵袭和迁移，并促进大肠癌细胞在LPS刺激下的凋亡。提示其可作为大肠癌的潜在诊断标志物和治疗靶点。
Background Colorectal cancer (CRC) is a leading cancer and a major cause of death. Lipopolysaccharide (LPS), an abundant component in gut microbiome, is involved in CRC progression and metastasis, potentially through regulating the miRNA composition of CRC-derived exosomes. In this study, we aimed to identify miRNA species in exosome which regulates CRC progression after LPS stimulation. Results Firstly, we discovered a shift of miRNA profile in CRC exosome after LPS stimulation. Among the differentially expressed miRNAs, we identified miR-200c-3p as a potential key regulator of CRC progression and metastasis. Retrospective analysis revealed that miR-200c-3p was elevated in CRC tumor tissues, but decreased in the serum exosome in CRC patients. In vitro experiments demonstrated that exosomal miR-200c-3p expression did not influence CRC cell proliferation, but negatively regulated their capacity of migration and invasion in the presence of LPS. miR-200c-3p level in exosome influenced exosomal expression ofZinc finger E-box-binding homeobox-1(ZEB-1)mRNA, one of the miR-200c targets which affects migration and invasion capacity, and further altered ZEB-1 protein expression in CRC cell. In addition, exosomal miR-200c-3p promotes apoptosis of HCT-116 cells. Conclusions Our findings indicate that exosomal miR-200c-3p inhibits CRC migration and invasion, and promotes their apoptosis after LPS stimulation. It is suggested as a potential diagnostic marker and therapeutic target of CRC.