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

Abstract

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.

Keywords

• colorectal cancer
• exosomes
• FBXW7
• microRNA‐19b
• stemness