MicroRNA-624-mediated ARRDC3/YAP/HIF1α axis enhances esophageal squamous cell carcinoma cell resistance to cisplatin and paclitaxel

Development of chemoresistance remains a major challenge in treating patients suffering from esophageal squamous cell carcinoma (ESCC), despite treatment advances. MicroRNAs (miRNAs) have been shown to play critical roles in the regulation of ESCC cell chemoresistance. Here, we aimed to investigate...

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Autores principales:	Jie Yan, Litong Shi, Shan Lin, Yi Li
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	esophageal squamous cell carcinoma microrna-624 arrestin domain-containing 3 yes-associated protein hypoxia-inducible factor-1α cisplatin paclitaxel Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/56ca190f963944ff9654cde9dc46b769
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spelling	oai:doaj.org-article:56ca190f963944ff9654cde9dc46b7692021-11-04T15:51:53ZMicroRNA-624-mediated ARRDC3/YAP/HIF1α axis enhances esophageal squamous cell carcinoma cell resistance to cisplatin and paclitaxel2165-59792165-598710.1080/21655979.2021.1938497https://doaj.org/article/56ca190f963944ff9654cde9dc46b7692021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1938497https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Development of chemoresistance remains a major challenge in treating patients suffering from esophageal squamous cell carcinoma (ESCC), despite treatment advances. MicroRNAs (miRNAs) have been shown to play critical roles in the regulation of ESCC cell chemoresistance. Here, we aimed to investigate the role of miR-624 in ESCC and its molecular mechanism in mediating the resistance of ESCC cells to two common chemotherapeutic drugs, cisplatin (CIS) and paclitaxel (PT). Expression patterns of miR-624, arrestin domain-containing 3 (ARRDC3), Yes-associated protein (YAP), and hypoxia-inducible factor-1α (HIF1α) in ESCC tissues and cell lines were identified using RT-qPCR and Western blot analysis. The binding affinities with the miR-624/ARRDC3/YAP/HIF1α axis were characterized. The chemotherapy-sensitive cell line KYSE150 and chemotherapy-resistant cell line KYSE410 were transfected with an overexpression plasmid or shRNA to study the effect of miR-624/ARRDC3/YAP/HIF1α axis on ESCC cell resistance to CIS and PT. Their in vivo effects on resistance to PT were assessed in tumor-bearing nude mice. High expression of miR-624, YAP and HIF1α, and low expression of ARRDC3 were observed in ESCC tissues and cell lines. miR-624 presented with higher expression in KYSE410 than in KYSE150 cells. miR-624 downregulated ARRDC3 to increase YAP and HIF1α expression so as to enhance ESCC cell resistance to CIS and PT in vitro and in vivo. Taken together, these data indicate an important role for miR-624 in promoting the chemoresistance of ESCC cells, highlighting a potential strategy to overcome drug resistance in ESCC treatment. miR-624 targets ARRDC3 to inhibit its expression, and consequently upregulates YAP expression by inhibiting degradation of YAP. By this mechanism, HIF1α expression is upregulated and the HIF1α signaling pathway is activated. ESCC cell chemotherapy resistance is eventually increased.Jie YanLitong ShiShan LinYi LiTaylor & Francis Grouparticleesophageal squamous cell carcinomamicrorna-624arrestin domain-containing 3yes-associated proteinhypoxia-inducible factor-1αcisplatinpaclitaxelBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 1, Pp 5334-5347 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	esophageal squamous cell carcinoma microrna-624 arrestin domain-containing 3 yes-associated protein hypoxia-inducible factor-1α cisplatin paclitaxel Biotechnology TP248.13-248.65
spellingShingle	esophageal squamous cell carcinoma microrna-624 arrestin domain-containing 3 yes-associated protein hypoxia-inducible factor-1α cisplatin paclitaxel Biotechnology TP248.13-248.65 Jie Yan Litong Shi Shan Lin Yi Li MicroRNA-624-mediated ARRDC3/YAP/HIF1α axis enhances esophageal squamous cell carcinoma cell resistance to cisplatin and paclitaxel
description	Development of chemoresistance remains a major challenge in treating patients suffering from esophageal squamous cell carcinoma (ESCC), despite treatment advances. MicroRNAs (miRNAs) have been shown to play critical roles in the regulation of ESCC cell chemoresistance. Here, we aimed to investigate the role of miR-624 in ESCC and its molecular mechanism in mediating the resistance of ESCC cells to two common chemotherapeutic drugs, cisplatin (CIS) and paclitaxel (PT). Expression patterns of miR-624, arrestin domain-containing 3 (ARRDC3), Yes-associated protein (YAP), and hypoxia-inducible factor-1α (HIF1α) in ESCC tissues and cell lines were identified using RT-qPCR and Western blot analysis. The binding affinities with the miR-624/ARRDC3/YAP/HIF1α axis were characterized. The chemotherapy-sensitive cell line KYSE150 and chemotherapy-resistant cell line KYSE410 were transfected with an overexpression plasmid or shRNA to study the effect of miR-624/ARRDC3/YAP/HIF1α axis on ESCC cell resistance to CIS and PT. Their in vivo effects on resistance to PT were assessed in tumor-bearing nude mice. High expression of miR-624, YAP and HIF1α, and low expression of ARRDC3 were observed in ESCC tissues and cell lines. miR-624 presented with higher expression in KYSE410 than in KYSE150 cells. miR-624 downregulated ARRDC3 to increase YAP and HIF1α expression so as to enhance ESCC cell resistance to CIS and PT in vitro and in vivo. Taken together, these data indicate an important role for miR-624 in promoting the chemoresistance of ESCC cells, highlighting a potential strategy to overcome drug resistance in ESCC treatment. miR-624 targets ARRDC3 to inhibit its expression, and consequently upregulates YAP expression by inhibiting degradation of YAP. By this mechanism, HIF1α expression is upregulated and the HIF1α signaling pathway is activated. ESCC cell chemotherapy resistance is eventually increased.
format	article
author	Jie Yan Litong Shi Shan Lin Yi Li
author_facet	Jie Yan Litong Shi Shan Lin Yi Li
author_sort	Jie Yan
title	MicroRNA-624-mediated ARRDC3/YAP/HIF1α axis enhances esophageal squamous cell carcinoma cell resistance to cisplatin and paclitaxel
title_short	MicroRNA-624-mediated ARRDC3/YAP/HIF1α axis enhances esophageal squamous cell carcinoma cell resistance to cisplatin and paclitaxel
title_full	MicroRNA-624-mediated ARRDC3/YAP/HIF1α axis enhances esophageal squamous cell carcinoma cell resistance to cisplatin and paclitaxel
title_fullStr	MicroRNA-624-mediated ARRDC3/YAP/HIF1α axis enhances esophageal squamous cell carcinoma cell resistance to cisplatin and paclitaxel
title_full_unstemmed	MicroRNA-624-mediated ARRDC3/YAP/HIF1α axis enhances esophageal squamous cell carcinoma cell resistance to cisplatin and paclitaxel
title_sort	microrna-624-mediated arrdc3/yap/hif1α axis enhances esophageal squamous cell carcinoma cell resistance to cisplatin and paclitaxel
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/56ca190f963944ff9654cde9dc46b769
work_keys_str_mv	AT jieyan microrna624mediatedarrdc3yaphif1aaxisenhancesesophagealsquamouscellcarcinomacellresistancetocisplatinandpaclitaxel AT litongshi microrna624mediatedarrdc3yaphif1aaxisenhancesesophagealsquamouscellcarcinomacellresistancetocisplatinandpaclitaxel AT shanlin microrna624mediatedarrdc3yaphif1aaxisenhancesesophagealsquamouscellcarcinomacellresistancetocisplatinandpaclitaxel AT yili microrna624mediatedarrdc3yaphif1aaxisenhancesesophagealsquamouscellcarcinomacellresistancetocisplatinandpaclitaxel
_version_	1718444715155652608

MicroRNA-624-mediated ARRDC3/YAP/HIF1α axis enhances esophageal squamous cell carcinoma cell resistance to cisplatin and paclitaxel

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