Abstract
BackgroundColorectal 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.ResultsFirstly, 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.ConclusionsOur 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.
Highlights
Colorectal cancer (CRC) is a leading cancer and a major cause of death
LPS did not change the morphorlogy of HCT-116 cellderived exosome After 24 h LPS treatment, we extracted exosomes from HCT-116 cells and observed their morphology by transmission electron microscopy (TEM)
LPS induced the alteration of the miRNA profile in HCT116 cell-derived exosome We further attempted to identify the miRNA profile change in the exosomes derived from LPS-treated cells
Summary
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. We aimed to identify miRNA species in exosome which regulates CRC progression after LPS stimulation. Colorectal cancer (CRC) is the third most common cancer in the world and causes more than 600,000 deaths every year, in elderly group [1, 2]. Exosome has been identified as a major regulator of CRC progression [14]. It is of high interest to figure out whether LPS can regulate CRC progression and metastasis through specific miRNA species in CRCsecreted exosome
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