Folic Acid–Modified miR-491-5p–Loaded ZIF-8 Nanoparticles Inhibit Castration-Resistant Prostate Cancer by Regulating the Expression of EPHX1

Epoxide hydrolase 1 (EPHX1) has been reported to be related to the development of several tumors. However, the regulation of castration-resistant prostate cancer (CRPC) development by EPHX1 has not been reported. We used proteomic technology and found that the EPHX1 protein was highly expressed in C...

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Autores principales:	Guanqun Ju, Bing Liu, Mingfei Ji, Rui Jin, Xiaojian Xu, Yongshuang Xiao, Jie Li, Dongliang Xu, Yuhua Huang, Jianquan Hou
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	miR-491-5p ZIF-8 EPHX1 drug nanocarrier castration-resistant prostate cancer Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/ce02dd09209a47eeaaa0b1b248ba4998
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spelling	oai:doaj.org-article:ce02dd09209a47eeaaa0b1b248ba49982021-11-22T06:39:22ZFolic Acid–Modified miR-491-5p–Loaded ZIF-8 Nanoparticles Inhibit Castration-Resistant Prostate Cancer by Regulating the Expression of EPHX12296-418510.3389/fbioe.2021.706536https://doaj.org/article/ce02dd09209a47eeaaa0b1b248ba49982021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fbioe.2021.706536/fullhttps://doaj.org/toc/2296-4185Epoxide hydrolase 1 (EPHX1) has been reported to be related to the development of several tumors. However, the regulation of castration-resistant prostate cancer (CRPC) development by EPHX1 has not been reported. We used proteomic technology and found that the EPHX1 protein was highly expressed in CRPC tissues and the CRPC cell line C4-2. We performed screening and found that EPHX1 is a direct target of miR-491-5p. High miR-491-5p expression significantly reduced the EPHX1 level in C4-2 cells and inhibited C4-2 cell proliferation and migration. Zeolite imidazolate framework-8 (ZIF-8) has good thermal stability, a simple synthesis method, tumor site stability, and specific acid responsiveness. We synthesized ZIF-8 nanodrug vectors to deliver miR-491-5p into C4-2 cells. After loading miR-491-5p into ZIF-8, we modified the ZIF-8 surface with folic acid (FA) as the target group (FA@ZIF-8). Our synthesized nanodrug carrier showed less cytotoxicity to C4-2 cells even at 200 μg/ml. Modified FA could increase the efficiency of nanomaterial entry into C4-2 cells. FA@miR-491-5p@ZIF-8 could stably release miR-491-5p for a long period in both phosphate-buffered saline (pH 7.4) and acetate buffer (pH 4.8), and miR-491-5p was released faster at the beginning of the experiment in acetate buffer (pH 4.8). FA@miR-491-5p@ZIF-8 significantly reduced C4-2 cell proliferation and migration, and FA@miR-491-5p@ZIF-8 had a better effect than miR-491-5p alone. In vivo, FA@miR-491-5p@ZIF-8 significantly inhibited CRPC growth in nude mice. Overall, we verified that miR-491-4p regulated CRPC development by targeting EPHX1. The drug nanocarrier FA@miR-491-5p@ZIF-8 not only significantly reduced C4-2 CRPC cell proliferation and migration but also significantly inhibited CRPC growth. Our research provides a theoretical basis for treatment and treatment strategies for CRPC.Guanqun JuGuanqun JuBing LiuMingfei JiRui JinXiaojian XuYongshuang XiaoJie LiDongliang XuYuhua HuangJianquan HouJianquan HouFrontiers Media S.A.articlemiR-491-5pZIF-8EPHX1drug nanocarriercastration-resistant prostate cancerBiotechnologyTP248.13-248.65ENFrontiers in Bioengineering and Biotechnology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	miR-491-5p ZIF-8 EPHX1 drug nanocarrier castration-resistant prostate cancer Biotechnology TP248.13-248.65
spellingShingle	miR-491-5p ZIF-8 EPHX1 drug nanocarrier castration-resistant prostate cancer Biotechnology TP248.13-248.65 Guanqun Ju Guanqun Ju Bing Liu Mingfei Ji Rui Jin Xiaojian Xu Yongshuang Xiao Jie Li Dongliang Xu Yuhua Huang Jianquan Hou Jianquan Hou Folic Acid–Modified miR-491-5p–Loaded ZIF-8 Nanoparticles Inhibit Castration-Resistant Prostate Cancer by Regulating the Expression of EPHX1
description	Epoxide hydrolase 1 (EPHX1) has been reported to be related to the development of several tumors. However, the regulation of castration-resistant prostate cancer (CRPC) development by EPHX1 has not been reported. We used proteomic technology and found that the EPHX1 protein was highly expressed in CRPC tissues and the CRPC cell line C4-2. We performed screening and found that EPHX1 is a direct target of miR-491-5p. High miR-491-5p expression significantly reduced the EPHX1 level in C4-2 cells and inhibited C4-2 cell proliferation and migration. Zeolite imidazolate framework-8 (ZIF-8) has good thermal stability, a simple synthesis method, tumor site stability, and specific acid responsiveness. We synthesized ZIF-8 nanodrug vectors to deliver miR-491-5p into C4-2 cells. After loading miR-491-5p into ZIF-8, we modified the ZIF-8 surface with folic acid (FA) as the target group (FA@ZIF-8). Our synthesized nanodrug carrier showed less cytotoxicity to C4-2 cells even at 200 μg/ml. Modified FA could increase the efficiency of nanomaterial entry into C4-2 cells. FA@miR-491-5p@ZIF-8 could stably release miR-491-5p for a long period in both phosphate-buffered saline (pH 7.4) and acetate buffer (pH 4.8), and miR-491-5p was released faster at the beginning of the experiment in acetate buffer (pH 4.8). FA@miR-491-5p@ZIF-8 significantly reduced C4-2 cell proliferation and migration, and FA@miR-491-5p@ZIF-8 had a better effect than miR-491-5p alone. In vivo, FA@miR-491-5p@ZIF-8 significantly inhibited CRPC growth in nude mice. Overall, we verified that miR-491-4p regulated CRPC development by targeting EPHX1. The drug nanocarrier FA@miR-491-5p@ZIF-8 not only significantly reduced C4-2 CRPC cell proliferation and migration but also significantly inhibited CRPC growth. Our research provides a theoretical basis for treatment and treatment strategies for CRPC.
format	article
author	Guanqun Ju Guanqun Ju Bing Liu Mingfei Ji Rui Jin Xiaojian Xu Yongshuang Xiao Jie Li Dongliang Xu Yuhua Huang Jianquan Hou Jianquan Hou
author_facet	Guanqun Ju Guanqun Ju Bing Liu Mingfei Ji Rui Jin Xiaojian Xu Yongshuang Xiao Jie Li Dongliang Xu Yuhua Huang Jianquan Hou Jianquan Hou
author_sort	Guanqun Ju
title	Folic Acid–Modified miR-491-5p–Loaded ZIF-8 Nanoparticles Inhibit Castration-Resistant Prostate Cancer by Regulating the Expression of EPHX1
title_short	Folic Acid–Modified miR-491-5p–Loaded ZIF-8 Nanoparticles Inhibit Castration-Resistant Prostate Cancer by Regulating the Expression of EPHX1
title_full	Folic Acid–Modified miR-491-5p–Loaded ZIF-8 Nanoparticles Inhibit Castration-Resistant Prostate Cancer by Regulating the Expression of EPHX1
title_fullStr	Folic Acid–Modified miR-491-5p–Loaded ZIF-8 Nanoparticles Inhibit Castration-Resistant Prostate Cancer by Regulating the Expression of EPHX1
title_full_unstemmed	Folic Acid–Modified miR-491-5p–Loaded ZIF-8 Nanoparticles Inhibit Castration-Resistant Prostate Cancer by Regulating the Expression of EPHX1
title_sort	folic acid–modified mir-491-5p–loaded zif-8 nanoparticles inhibit castration-resistant prostate cancer by regulating the expression of ephx1
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ce02dd09209a47eeaaa0b1b248ba4998
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Folic Acid–Modified miR-491-5p–Loaded ZIF-8 Nanoparticles Inhibit Castration-Resistant Prostate Cancer by Regulating the Expression of EPHX1

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