The circRAB3IP Mediated by eIF4A3 and LEF1 Contributes to Enzalutamide Resistance in Prostate Cancer by Targeting miR-133a-3p/miR-133b/SGK1 Pathway

An increasing number of studies have shown that circRNAs are closely related to the carcinogenesis and development of prostate cancer (PCa). However, little is known about the effect of the biological functions of circRNAs on the enzalutamide resistance of PCa. Through bioinformatic analysis and exp...

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Autores principales:	Dong Chen, Yaqin Wang, Feiya Yang, Adili Keranmu, Qingxin Zhao, Liyuan Wu, Sujun Han, Nianzeng Xing
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	circRAB3IP eIF4A3 LEF1 SGK1 enzalutamide resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a82719dc38454164afc29a5855342ada
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spelling	oai:doaj.org-article:a82719dc38454164afc29a5855342ada2021-11-15T05:43:21ZThe circRAB3IP Mediated by eIF4A3 and LEF1 Contributes to Enzalutamide Resistance in Prostate Cancer by Targeting miR-133a-3p/miR-133b/SGK1 Pathway2234-943X10.3389/fonc.2021.752573https://doaj.org/article/a82719dc38454164afc29a5855342ada2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.752573/fullhttps://doaj.org/toc/2234-943XAn increasing number of studies have shown that circRNAs are closely related to the carcinogenesis and development of prostate cancer (PCa). However, little is known about the effect of the biological functions of circRNAs on the enzalutamide resistance of PCa. Through bioinformatic analysis and experiments, we investigated the expression pattern of circRNAs in enzalutamide-resistant PCa cells. Quantitative real-time PCR was used to detect the expression of circRAB3IP, and plasmids that knock down or overexpress circRAB3IP were used to evaluate its effect on the enzalutamide sensitivity of PCa cells. Mechanistically, we explored the potential regulatory effects of eIF4A3 and LEF1 on the biogenesis of circRAB3IP. Our in vivo and in vitro data indicated that increased expression of circRAB3IP was found in enzalutamide-resistant PCa, and knockdown of circRAB3IP significantly enhanced enzalutamide sensitivity in PCa cells. However, upregulation of circRAB3IP resulted in the opposite effects. Further mechanistic research demonstrated that circRAB3IP could regulate the expression of serum and glucocorticoid-regulated kinase 1 (SGK1) by serving as a sponge that directly targets miR-133a-3p/miR-133b. Then, we showed that circRAB3IP partially exerted its biological functions via SGK1 signaling. Furthermore, we discovered that eIF4A3 and LEF1 might increase circRAB3IP expression in PCa.Dong ChenDong ChenYaqin WangFeiya YangFeiya YangAdili KeranmuAdili KeranmuQingxin ZhaoQingxin ZhaoLiyuan WuLiyuan WuSujun HanSujun HanNianzeng XingNianzeng XingFrontiers Media S.A.articlecircRAB3IPeIF4A3LEF1SGK1enzalutamide resistanceNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	circRAB3IP eIF4A3 LEF1 SGK1 enzalutamide resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	circRAB3IP eIF4A3 LEF1 SGK1 enzalutamide resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Dong Chen Dong Chen Yaqin Wang Feiya Yang Feiya Yang Adili Keranmu Adili Keranmu Qingxin Zhao Qingxin Zhao Liyuan Wu Liyuan Wu Sujun Han Sujun Han Nianzeng Xing Nianzeng Xing The circRAB3IP Mediated by eIF4A3 and LEF1 Contributes to Enzalutamide Resistance in Prostate Cancer by Targeting miR-133a-3p/miR-133b/SGK1 Pathway
description	An increasing number of studies have shown that circRNAs are closely related to the carcinogenesis and development of prostate cancer (PCa). However, little is known about the effect of the biological functions of circRNAs on the enzalutamide resistance of PCa. Through bioinformatic analysis and experiments, we investigated the expression pattern of circRNAs in enzalutamide-resistant PCa cells. Quantitative real-time PCR was used to detect the expression of circRAB3IP, and plasmids that knock down or overexpress circRAB3IP were used to evaluate its effect on the enzalutamide sensitivity of PCa cells. Mechanistically, we explored the potential regulatory effects of eIF4A3 and LEF1 on the biogenesis of circRAB3IP. Our in vivo and in vitro data indicated that increased expression of circRAB3IP was found in enzalutamide-resistant PCa, and knockdown of circRAB3IP significantly enhanced enzalutamide sensitivity in PCa cells. However, upregulation of circRAB3IP resulted in the opposite effects. Further mechanistic research demonstrated that circRAB3IP could regulate the expression of serum and glucocorticoid-regulated kinase 1 (SGK1) by serving as a sponge that directly targets miR-133a-3p/miR-133b. Then, we showed that circRAB3IP partially exerted its biological functions via SGK1 signaling. Furthermore, we discovered that eIF4A3 and LEF1 might increase circRAB3IP expression in PCa.
format	article
author	Dong Chen Dong Chen Yaqin Wang Feiya Yang Feiya Yang Adili Keranmu Adili Keranmu Qingxin Zhao Qingxin Zhao Liyuan Wu Liyuan Wu Sujun Han Sujun Han Nianzeng Xing Nianzeng Xing
author_facet	Dong Chen Dong Chen Yaqin Wang Feiya Yang Feiya Yang Adili Keranmu Adili Keranmu Qingxin Zhao Qingxin Zhao Liyuan Wu Liyuan Wu Sujun Han Sujun Han Nianzeng Xing Nianzeng Xing
author_sort	Dong Chen
title	The circRAB3IP Mediated by eIF4A3 and LEF1 Contributes to Enzalutamide Resistance in Prostate Cancer by Targeting miR-133a-3p/miR-133b/SGK1 Pathway
title_short	The circRAB3IP Mediated by eIF4A3 and LEF1 Contributes to Enzalutamide Resistance in Prostate Cancer by Targeting miR-133a-3p/miR-133b/SGK1 Pathway
title_full	The circRAB3IP Mediated by eIF4A3 and LEF1 Contributes to Enzalutamide Resistance in Prostate Cancer by Targeting miR-133a-3p/miR-133b/SGK1 Pathway
title_fullStr	The circRAB3IP Mediated by eIF4A3 and LEF1 Contributes to Enzalutamide Resistance in Prostate Cancer by Targeting miR-133a-3p/miR-133b/SGK1 Pathway
title_full_unstemmed	The circRAB3IP Mediated by eIF4A3 and LEF1 Contributes to Enzalutamide Resistance in Prostate Cancer by Targeting miR-133a-3p/miR-133b/SGK1 Pathway
title_sort	circrab3ip mediated by eif4a3 and lef1 contributes to enzalutamide resistance in prostate cancer by targeting mir-133a-3p/mir-133b/sgk1 pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a82719dc38454164afc29a5855342ada
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The circRAB3IP Mediated by eIF4A3 and LEF1 Contributes to Enzalutamide Resistance in Prostate Cancer by Targeting miR-133a-3p/miR-133b/SGK1 Pathway

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