Exosomal microRNA-19b targets FBXW7 to promote colorectal cancer stem cell stemness and induce resistance to radiotherapy

Abstract

Colorectal cancer (CRC) continues to be one of the most malignant cancers with a high mortality rate to date. Promoting the radio-responsiveness of CRC is of great importance for local control and prognosis. In this study, we examined the roles of exosomal microRNA-19b (miR-19b) in CRC radioresistance. The regulatory role of miR-19b in CRC stem cells and radiotherapy-resistant cells was determined using miRNA microarray analysis, and its prognostic value was probed using the TCGA database. It was found that miR-19b was overexpressed in CRC tissues, which indicated a poor prognosis. CRC-derived exosomes (EXOs) enhanced the radio-resistance and stemness properties of CRC cells via delivery of miR-19b in vitro and in vivo. FBXW7 was identified as a putative target of miR-19b. On the contrary, reintroduction of FBXW7 reversed the effects of miR-19b on radioresistance and stemness properties. Furthermore, the Wnt/β-catenin pathway activity was elevated in CRC cells upon EXOs treatment, decreased after miR-19b downregulation, and increased again after FBXW7 downregulation. These results suggest that miR-19b inhibition could enhance the efficacy of radiotherapy while reducing the stemness properties, thus presenting a promising strategy for sensitizing CRC cells to radiotherapy.