Home HOME Neoplasma 2021 Neoplasma Vol.68, No.1, p.108–118, 2021

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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

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Neoplasma Vol.68, No.1, p.108–118, 2021

Title: Exosomal transfer of circular RNA FBXW7 ameliorates the chemoresistance to oxaliplatin in colorectal cancer by sponging miR-18b-5p
Author: Yeqing Xu, Aizhu Qiu, Feng Peng, Xiangyun Tan, Jin Wang, Xiaosong Gong

Abstract: Circular RNA F-box and WD repeat domain containing 7 (Circ-FBXW7) has been revealed to involve 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 through 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

Keywords: circ-FBXW7; miR-18b-5p; oxaliplatin; exosome; colorectal cancer
Published online: 04-Nov-2020
Year: 2021, Volume: 68, Issue: 1 Page From: 108, Page To: 118

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