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. 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 of Zinc 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. 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.

中文翻译：

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外泌体 miR-200c-3p 负向调节脂多糖 (LPS) 刺激的结直肠癌 (CRC) 的迁移和侵袭。


结直肠癌（CRC）是一种主要癌症，也是主要的死亡原因。脂多糖 (LPS) 是肠道微生物组中丰富的成分，可能通过调节 CRC 衍生的外泌体的 miRNA 组成参与 CRC 的进展和转移。在这项研究中，我们的目的是鉴定外泌体中在 LPS 刺激后调节 CRC 进展的 miRNA 种类。首先，我们发现 LPS 刺激后 CRC 外泌体中 miRNA 谱发生变化。在差异表达的 miRNA 中，我们确定 miR-200c-3p 是 CRC 进展和转移的潜在关键调节因子。回顾性分析显示，miR-200c-3p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-200c-3p表达不影响CRC细胞增殖，但在LPS存在下负向调节其迁移和侵袭能力。外泌体中的 miR-200c-3p 水平影响锌指 E 盒结合同源盒-1 (ZEB-1) mRNA 的外泌体表达，ZEB-1 是影响迁移和侵袭能力的 miR-200c 靶标之一，并进一步改变了 ZEB-1 蛋白CRC细胞中的表达。此外，外泌体miR-200c-3p促进HCT-116细胞凋亡。我们的研究结果表明，外泌体 miR-200c-3p 抑制 CRC 迁移和侵袭，并在 LPS 刺激后促进其凋亡。它被建议作为结直肠癌的潜在诊断标志物和治疗靶点。