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

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...

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Autores principales:	Lu Jiang, Yan Zhang, Linghui Guo, Chaoyang Liu, Pan Wang, Weihong Ren
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Gastric cancer Reverse drug resistance Exosomal miR-107 HMGA2/mTOR/P-gp Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/3a8231fc73b34ce3bdb104eea40e9b89
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spelling	oai:doaj.org-article:3a8231fc73b34ce3bdb104eea40e9b892021-12-05T12:19:34ZExosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2/mTOR/P-gp pathway10.1186/s12885-021-09020-y1471-2407https://doaj.org/article/3a8231fc73b34ce3bdb104eea40e9b892021-12-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-09020-yhttps://doaj.org/toc/1471-2407Abstract 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 verified by exosomal inhibitor GW4896. Mechanistically, the reversal effect was mainly mediated by exosome-secreted miR-107 through downregulating the expression of target molecular HMGA2 and inhibiting HMGA2/mTOR/P-gp pathway, which were supported by results from luciferase reporter assay and rescue assay. Conclusions These findings demonstrated that exosome-transmitted miR-107 significantly enhanced the sensitivity of resistant gastric cancer cells to chemotherapeutic agents by mediating the HMGA2/mTOR/P-gp axis and exosomal miR-107 may be a novel target in gastric cancers treatment.Lu JiangYan ZhangLinghui GuoChaoyang LiuPan WangWeihong RenBMCarticleGastric cancerReverse drug resistanceExosomal miR-107HMGA2/mTOR/P-gpNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Gastric cancer Reverse drug resistance Exosomal miR-107 HMGA2/mTOR/P-gp Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Gastric cancer Reverse drug resistance Exosomal miR-107 HMGA2/mTOR/P-gp Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Lu Jiang Yan Zhang Linghui Guo Chaoyang Liu Pan Wang Weihong Ren Exosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2/mTOR/P-gp pathway
description	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 verified by exosomal inhibitor GW4896. Mechanistically, the reversal effect was mainly mediated by exosome-secreted miR-107 through downregulating the expression of target molecular HMGA2 and inhibiting HMGA2/mTOR/P-gp pathway, which were supported by results from luciferase reporter assay and rescue assay. Conclusions These findings demonstrated that exosome-transmitted miR-107 significantly enhanced the sensitivity of resistant gastric cancer cells to chemotherapeutic agents by mediating the HMGA2/mTOR/P-gp axis and exosomal miR-107 may be a novel target in gastric cancers treatment.
format	article
author	Lu Jiang Yan Zhang Linghui Guo Chaoyang Liu Pan Wang Weihong Ren
author_facet	Lu Jiang Yan Zhang Linghui Guo Chaoyang Liu Pan Wang Weihong Ren
author_sort	Lu Jiang
title	Exosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2/mTOR/P-gp pathway
title_short	Exosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2/mTOR/P-gp pathway
title_full	Exosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2/mTOR/P-gp pathway
title_fullStr	Exosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2/mTOR/P-gp pathway
title_full_unstemmed	Exosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2/mTOR/P-gp pathway
title_sort	exosomal microrna-107 reverses chemotherapeutic drug resistance of gastric cancer cells through hmga2/mtor/p-gp pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/3a8231fc73b34ce3bdb104eea40e9b89
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Exosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2/mTOR/P-gp pathway

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