Exosomal transfer of circular RNA FBXW7 ameliorates the chemoresistance to oxaliplatin in colorectal cancer by sponging miR-18b-5p

Rok, strany: 2021, 108 - 118

Circular RNA F-box and WD repeat domain containing 7 (circ-FBXW7) has been revealed to be involved in the tumorigenesis of colorectal cancer (CRC). Exosomes are critical mediators of intercellular communication. However, the role of exosomal circ-FBXW7 in the CRC oxaliplatin resistance remains unknown. Cell viability, apoptosis, motility, and drug efflux were measured by the cell counting kit-8 assay, flow cytometry, transwell assay, and atomic absorption spectrophotometry, respectively. The expression of circ-FBXW7 and microRNA (miR)-18b-5p was detected using the quantitative real-time polymerase chain reaction. Western blot was used to determine multidrug resistance protein 1 (MRP1), myeloid cell leukemia-1 (MCL-1), CD9, CD63, Caspase3, E-cadherin, and N-cadherin. Exosomes were isolated and captured using the ultracentrifugation method and transmission electron microscopy. The interaction between circ-FBXW7 and miR-18b-5p was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. In vivo experiments were conducted using the murine xenograft model. Our results showed that circ-FBXW7 was decreased in oxaliplatin-resistant CRC patients and cells. circ-FBXW7 was secreted by circ-FBXW7-transfected FHC cells and could be transferred to resistant CRC cells through the exosome secretion. Subsequently, in vitro and in vivo studies demonstrated exosomal circ-FBXW7 led resistant cells sensitive to oxaliplatin, increased the oxaliplatin-induced apoptosis, inhibited oxaliplatin-induced epithelial-mesenchymal transition, and suppressed oxaliplatin efflux. miR-18b-5p was increased in oxaliplatin-resistant CRC patients and cells and was confirmed to be a target of circ-FBXW7. Immediately, the rescue assay showed exosome-mediated transfer of circ-FBXW7 enhanced oxaliplatin sensitivity by binding to miR-18b-5p in vitro and in vivo. To conclude, the circ-FBXW7 delivery by exosomes could ameliorate chemoresistance to oxaliplatin in CRC by directly binding to miR-128-3p, suggesting a promising therapeutic strategy for oxaliplatin-resistant CRC patients.

ISO 690:

Xu, Y., Qiu, A., Peng, F., Tan, X., Wang, J., Gong, X. 2021. Exosomal transfer of circular RNA FBXW7 ameliorates the chemoresistance to oxaliplatin in colorectal cancer by sponging miR-18b-5p. In NEOPLASMA, vol. 68, no.1, pp. 108-118. 0028-2685. DOI: https://doi.org/10.4149/neo_2020_200417N414

APA:

Xu, Y., Qiu, A., Peng, F., Tan, X., Wang, J., Gong, X. (2021). Exosomal transfer of circular RNA FBXW7 ameliorates the chemoresistance to oxaliplatin in colorectal cancer by sponging miR-18b-5p. NEOPLASMA, 68(1), 108-118. 0028-2685. DOI: https://doi.org/10.4149/neo_2020_200417N414

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