Affiliation:
1. The First Affiliated Hospital of USTC, University of Science and Technology of China
2. The First Affiliated Hospital of Anhui University of Chinese Medicine
Abstract
Abstract
sEVs are extracellular vesicles with nanoscale bilayer membranes that deliver cell-specific proteins and nucleic acids (including mRNA and miRNA) to regulate intracellular signaling pathways. The development of hepatic fibrosis is closely related to sEV and its miRNA, which regulate the activation, proliferation, apoptosis, and migration of hepatic stellate cells. In this study, we report on the regulation of human hepatic stellate cell (HSC) LX-2 cell line by sEVs derived from serum of liver cancer patients through miR-122 and its potential signaling pathway. The effect of miR-122 on mRNA and protein expression of fibrosis markers was evaluated in human hepatic stellate cell LX-2 cell line transfected with miR-122 mimics or added serum-derived sEVs from liver cancer patients using QRT-PCR and western blot analysis. The effect of AMPK on LX-2 cell activation was validated using metformin or AMPK inhibitor. Results showed that miRNA-122 was expressed at low levels in activated LX-2 cells, but serum-derived sEVs and miR-122 mimics from liver cancer patients up-regulated miR-122 levels in activated LX-2 cells and reduced the expression of fibrosis marker proteins. The phosphorylation of AMPK decreased after activation of LX-2 cells, and the level of miR-122 was positively correlated with the phosphorylation of AMPK upon verification, suggesting that sEVs derived from serum of liver cancer patients can up-regulate miR-122 levels in LX-2 cells, change the energy status of cells, and inhibit the activation of HSC. This finding may provide an explanation for the reduced degree of fibrosis observed in HCC patients.
Publisher
Research Square Platform LLC
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