期刊
BMC MOLECULAR AND CELL BIOLOGY
卷 21, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12860-020-00291-0
关键词
Colorectal carcinoma; Lipopolysaccharide; miR-200c-3p; Exosome; ZEB-1
类别
资金
- Research Foundation of Ruijin North Hospital [2015ZY06]
- 3-year Clinical Skill and Innovation program of Shanghai Shenkang Hospital Development Center [16CR2064B, SHDC12015909]
- Shanghai Charity Cancer Research Center
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.
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