Circ_0092367 Inhibits EMT and Gemcitabine Resistance in Pancreatic Cancer via Regulating the miR-1206/ESRP1 Axis

Gemcitabine is the first-line treatment for patients with pancreatic cancer (PC), yet most patients develop resistance to gemcitabine. Recent studies showed that circular RNAs (circRNAs) have important regulatory roles in PC progression and chemoresistance. In this study, the ability of circRNA circ...

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Autores principales:	Shuo Yu, Min Wang, Hang Zhang, Xingjun Guo, Renyi Qin
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	circular RNA gemcitabine EMT pancreatic cancer Genetics QH426-470
Acceso en línea:	https://doaj.org/article/aa3cb364678e4a638dbe266b8aa7f540
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spelling	oai:doaj.org-article:aa3cb364678e4a638dbe266b8aa7f5402021-11-25T17:40:58ZCirc_0092367 Inhibits EMT and Gemcitabine Resistance in Pancreatic Cancer via Regulating the miR-1206/ESRP1 Axis10.3390/genes121117012073-4425https://doaj.org/article/aa3cb364678e4a638dbe266b8aa7f5402021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1701https://doaj.org/toc/2073-4425Gemcitabine is the first-line treatment for patients with pancreatic cancer (PC), yet most patients develop resistance to gemcitabine. Recent studies showed that circular RNAs (circRNAs) have important regulatory roles in PC progression and chemoresistance. In this study, the ability of circRNA circ_0092367 to enhance gemcitabine efficacy was tested and the underlying molecular mechanism of circ_0092367 was investigated. The expression levels of circ_0092367, miR-1206, and ESRP1 were measured using qRT-PCR experiments. The effects of circ_0092367, miR-1206, and ESRP1 on PC cell lines exposed to gemcitabine were examined by CCK-8 assays. We performed luciferase assays to determine the relationship between circ_0092367 and miR-1206 and between miR-1206 and ESRP1. We demonstrated that circ_0092367 was significantly downregulated in PC tissues and cell lines, and a high expression of circ_0092367 was associated with improved survival in patients with PC. Gain- and loss-of-function assays revealed that circ_0092367 inhibited epithelial–mesenchymal transition (EMT) phenotypes and sensitized PC cells to gemcitabine treatment in vitro and in vivo. Cytoplasmic circ_0092367 could directly repress the levels of miR-1206 and thus upregulate the expression of ESRP1, thereby inhibiting EMT and enhancing the sensitivity of PC cells to gemcitabine treatment. Our findings show that circ_0092367 plays a crucial role in sensitizing PC cells to gemcitabine by modulating the miR-1206/ESRP1 axis, highlighting its potential as a valuable therapeutic target in PC patients.Shuo YuMin WangHang ZhangXingjun GuoRenyi QinMDPI AGarticlecircular RNAgemcitabineEMTpancreatic cancerGeneticsQH426-470ENGenes, Vol 12, Iss 1701, p 1701 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	circular RNA gemcitabine EMT pancreatic cancer Genetics QH426-470
spellingShingle	circular RNA gemcitabine EMT pancreatic cancer Genetics QH426-470 Shuo Yu Min Wang Hang Zhang Xingjun Guo Renyi Qin Circ_0092367 Inhibits EMT and Gemcitabine Resistance in Pancreatic Cancer via Regulating the miR-1206/ESRP1 Axis
description	Gemcitabine is the first-line treatment for patients with pancreatic cancer (PC), yet most patients develop resistance to gemcitabine. Recent studies showed that circular RNAs (circRNAs) have important regulatory roles in PC progression and chemoresistance. In this study, the ability of circRNA circ_0092367 to enhance gemcitabine efficacy was tested and the underlying molecular mechanism of circ_0092367 was investigated. The expression levels of circ_0092367, miR-1206, and ESRP1 were measured using qRT-PCR experiments. The effects of circ_0092367, miR-1206, and ESRP1 on PC cell lines exposed to gemcitabine were examined by CCK-8 assays. We performed luciferase assays to determine the relationship between circ_0092367 and miR-1206 and between miR-1206 and ESRP1. We demonstrated that circ_0092367 was significantly downregulated in PC tissues and cell lines, and a high expression of circ_0092367 was associated with improved survival in patients with PC. Gain- and loss-of-function assays revealed that circ_0092367 inhibited epithelial–mesenchymal transition (EMT) phenotypes and sensitized PC cells to gemcitabine treatment in vitro and in vivo. Cytoplasmic circ_0092367 could directly repress the levels of miR-1206 and thus upregulate the expression of ESRP1, thereby inhibiting EMT and enhancing the sensitivity of PC cells to gemcitabine treatment. Our findings show that circ_0092367 plays a crucial role in sensitizing PC cells to gemcitabine by modulating the miR-1206/ESRP1 axis, highlighting its potential as a valuable therapeutic target in PC patients.
format	article
author	Shuo Yu Min Wang Hang Zhang Xingjun Guo Renyi Qin
author_facet	Shuo Yu Min Wang Hang Zhang Xingjun Guo Renyi Qin
author_sort	Shuo Yu
title	Circ_0092367 Inhibits EMT and Gemcitabine Resistance in Pancreatic Cancer via Regulating the miR-1206/ESRP1 Axis
title_short	Circ_0092367 Inhibits EMT and Gemcitabine Resistance in Pancreatic Cancer via Regulating the miR-1206/ESRP1 Axis
title_full	Circ_0092367 Inhibits EMT and Gemcitabine Resistance in Pancreatic Cancer via Regulating the miR-1206/ESRP1 Axis
title_fullStr	Circ_0092367 Inhibits EMT and Gemcitabine Resistance in Pancreatic Cancer via Regulating the miR-1206/ESRP1 Axis
title_full_unstemmed	Circ_0092367 Inhibits EMT and Gemcitabine Resistance in Pancreatic Cancer via Regulating the miR-1206/ESRP1 Axis
title_sort	circ_0092367 inhibits emt and gemcitabine resistance in pancreatic cancer via regulating the mir-1206/esrp1 axis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/aa3cb364678e4a638dbe266b8aa7f540
work_keys_str_mv	AT shuoyu circ0092367inhibitsemtandgemcitabineresistanceinpancreaticcancerviaregulatingthemir1206esrp1axis AT minwang circ0092367inhibitsemtandgemcitabineresistanceinpancreaticcancerviaregulatingthemir1206esrp1axis AT hangzhang circ0092367inhibitsemtandgemcitabineresistanceinpancreaticcancerviaregulatingthemir1206esrp1axis AT xingjunguo circ0092367inhibitsemtandgemcitabineresistanceinpancreaticcancerviaregulatingthemir1206esrp1axis AT renyiqin circ0092367inhibitsemtandgemcitabineresistanceinpancreaticcancerviaregulatingthemir1206esrp1axis
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Circ_0092367 Inhibits EMT and Gemcitabine Resistance in Pancreatic Cancer via Regulating the miR-1206/ESRP1 Axis

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