Suppressive effects of umbilical cord mesenchymal stem cell-derived exosomal miR-15a-5p on the progression of cholangiocarcinoma by inhibiting CHEK1 expression

Abstract

Currently, surgical extraction is the main therapy for cholangiocarcinoma (CCA) patients, but it’s highly susceptible to postsurgical complications and recurrence rate. Thus, we identified the suppressing roles of exosomal miR-15a-5p from umbilical cord mesenchymal stem cells (UCMSCs) in the EMT and metastasis of CCA. The microarray dataset GSE265566 was employed to determine the expression of CHEK1 in CCA tissues. The relationship of miR-15a-5p with CHEK1 was analyzed using bioinformatics tools and dual-luciferase reporter assay. The particle size of HUCMSCs-exo was detected by scanning electron microscopy and nanoparticle tracking analysis. The cellular and tumorous phenotypes were assessed through flow cytometry, CCK-8 assay, Transwell assay and the in vivo tumor xenograft experiments. CHEK1 was predicated to be markedly elevated in CCA. miR-15a-5p targeted CHEK1 and downregulated the expression of CHEK1. HUCMSCs-exo activated cell apoptosis but repressed the proliferative, invasive, and migratory potentials of CCA cells. After miR-15a-5p was silenced, HUCMSCs-exo presented an opposite effect in regulating CCA. Overexpression of miR-15a-5p promoted apoptosis but suppressed malignancy and tumorigenicity of CCA cells as well as EMT through downregulating CHEK1. Our data suggested that miR-15a-5p in HUCMSCs-exo suppresses EMT and metastasis of CCA through targeting downregulation of CHEK1.