tailieunhanh - Exosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2/mTOR/P-gp pathway

RNA cargo in exosomes, especially microRNAs (miRNAs), play an important role in the chemotherapy drug resistance of human cancers. However, the role and mechanism of exosomal miR-107 on multidrug resistance of gastric cancer cells was still not clear. In this study, we sought to explore whether exosomal miR-107 could reverse the resistance of gastric cancer cells to the chemotherapy drugs. | Jiang et al. BMC Cancer 2021 21 1290 https s12885-021-09020-y RESEARCH Open Access Exosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2 mTOR P-gp pathway Lu Jiang1 Yan Zhang1 Linghui Guo1 Chaoyang Liu1 Pan Wang2 and Weihong Ren3 Abstract Background RNA cargo in exosomes especially microRNAs miRNAs play an important role in the chemotherapy drug resistance of human cancers. However the role and mechanism of exosomal miR-107 on multidrug resistance of gastric cancer cells was still not clear. In this study we sought to explore whether exosomal miR-107 could reverse the resistance of gastric cancer cells to the chemotherapy drugs. Methods We extracted exosomes from sensitive SGC-7901 MGC-803 and resistant SGC-7901 5-FU gastric cancer cells by ultracentrifugation and the isolated exosomes were identified using transmission electron microscopy TEM and dynamic light scattering analysis DLS . The expression of miR-107 and high mobility group A2 HMGA2 were detected by real-time quantitative PCR RT-qPCR . MTT assay was used to investigate the effect of exosomes on gastric cancer cells growth in vitro. The uptake of exosomes by recipient cells were observed using a fluorescence microscope. The predicted target relationship between miR-107 and HMGA2 was verified by gauss-luciferase reporter assay. The expression of HMGA2 p-mTOR mTOR P-gp and other exosomal indicated marker proteins was detected by western blot. Results Our results indicated that the isolated exosomes were typically cup-like lipid bilayer membranes structure. SGC-7901 5-FU cells were cross-resistant to chemotherapy drug cisplatin CDDP and the sensitive cells-secreted exosomes drastically reversed the resistance of the resistant GC cells to the chemotherapeutic drugs which was veri- fied by exosomal inhibitor GW4896. Mechanistically the reversal effect was mainly mediated by exosome-secreted miR-107 through downregulating the expression of target