Loss of exosomal micro-RNA-200b-3p from hypoxia cancer-associated fibroblasts reduces sensitivity to 5-flourouracil in colorectal cancer through targeting high-mobility group box 3

• DOI: 10.3389/fonc.2022.920131
• Publication Date: 2022-10-05T08:06:31Z
• Authors: Hang Yuan; Bingchen Chen; Rui Chai; Wenjing Gong; Ziang Wan; Boan Zheng; Xinye Hu; Yang Guo; Shan Gao; Qiaoqiong Dai; Peng Yu; Shiliang Tu
• Keywords: Cancer-Associated Fibroblasts; Exosome; Viability assay; Tumor progression

Hypoxia-mediated tumor progression is a major problem in colorectal cancer (CRC). MicroRNA (miR)-200b-3p can attenuate tumorigenesis CRC, while exosomal miRNAs derived from cancer-associated fibroblasts (CAFs) promote progression. Nevertheless, the function of miR-200b-3p CAFs CRC remains unclear. In this study, and normal (NFs) were isolated adjacent tissues. Next, exosomes supernatants cultured under normoxia hypoxia. Cell viability was tested using cell counting kit-8 assay, flow cytometry used to assess apoptosis. invasion migration evaluated transwell assay. Dual-luciferase investigate relationship between high-mobility group box 3 (HMBG3). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) performed determine HMBG3 level. Our results found that level sharply reduced tissues compared Additionally, hypoxic normoxia. Exosomes weakened sensitivity cells 5-fluorouracil (5-FU) CAFs-derived exosomes. However, with upregulated increased addition, identified as downstream target cells, its overexpression partially reversed anti-tumor effect agomir on via mediation β-catenin/c-Myc axis. Furthermore, CAFs, therapeutic effects 5-FU vivo upregulation HMGB3 levels. Collectively, loss hypoxia by targeting HMGB3. Thus, our research outlines novel method for treatment CRC.