Cancer-derived exosomal-Alu RNA promotes colorectal cancer progression

Abstract

Abstract Inflammation plays a crucial role in cancer progression, but the relevance of the NLRP3 inflammasome remains unclear. Alu RNA is the first endogenous nucleic acid identified to activate the NLRP3 inflammasome. Here we show that Alu RNA can induce epithelial-to-mesenchymal transition (EMT) through NLRP3 inflammasome activation and releasing IL-1b in colorectal cancer (CRC) cells. Alu RNA is stored, transported and transferred to CRC cells by exosomes. Exosomal-Alu RNA promotes tumorigenesis by inducing invasion, metastasis and EMT through NLRP3 inflammasome activation. Corroborating this data, we found that the significantly increased expression of Alu RNA correlates with the induction of NLRP3 priming in human CRC patients. Furthermore, the expression level of Alu RNA from circulating exosomes correlate with CRC progression in preclinical model. These findings reveal the direct involvement of Alu RNA in cancer pathogenesis and their presence in CRC cell-derived exosomes could be used as non-invasive diagnostic biomarker.