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Circular RNA circ_0006168 enhances Taxol resistance in esophageal squamous cell carcinoma by regulating miR-194-5p/JMJD1C axis
BACKGROUND: Chemoresistance is one of the major obstacles for cancer therapy in the clinic. Circular RNAs (circRNAs) are involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and chemoresistance. This study aimed to explore the role and molecular mechanism of circ_0006168 in Taxo...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141117/ https://www.ncbi.nlm.nih.gov/pubmed/34022910 http://dx.doi.org/10.1186/s12935-021-01984-y |
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author | Qu, Fanyong Wang, Lina Wang, Caiyan Yu, Lingxia Zhao, Kaikai Zhong, Hao |
author_facet | Qu, Fanyong Wang, Lina Wang, Caiyan Yu, Lingxia Zhao, Kaikai Zhong, Hao |
author_sort | Qu, Fanyong |
collection | PubMed |
description | BACKGROUND: Chemoresistance is one of the major obstacles for cancer therapy in the clinic. Circular RNAs (circRNAs) are involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and chemoresistance. This study aimed to explore the role and molecular mechanism of circ_0006168 in Taxol resistance of ESCC. METHODS: The expression levels of circ_0006168, microRNA-194-5p (miR-194-5p) and jumonji domain containing 1C (JMJD1C) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The half-inhibition concentration (IC(50)) value of Taxol was evaluated by Cell Counting Kit-8 (CCK-8) assay. Cell proliferation was evaluated by CCK-8 and colony formation assays. Cell migration and invasion were detected by transwell assay. Cell apoptosis was determined by flow cytometry. The interaction between miR-194-5p and circ_0006168 or JMJD1C was predicted by bioinformatics analysis (Circinteractome and TargetScan) and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) and RNA pull-down assays. The mice xenograft model was established to investigate the roles of circ_0006168 in vivo. RESULTS: Circ_0006168 and JMJD1C were upregulated and miR-194-5p was downregulated in ESCC tissues, ESCC cells, and Taxol-resistant cells. Functionally, knockdown of circ_0006168 or JMJD1C increased Taxol sensitivity of ESCC in vitro via inhibiting cell proliferation, migration and invasion, and promoting apoptosis. Moreover, circ_0006168 could directly bind to miR-194-5p and JMJD1C was verified as a direct target of miR-194-5p. Mechanically, circ_0006168 was a sponge of miR-194-5p to regulate JMJD1C expression in ESCC cells. Furthermore, JMJD1C overexpression reversed the promotive effect of circ_0006168 knockdown on Taxol sensitivity. Besides, circ_0006168 silence suppressed tumor growth in vivo. CONCLUSION: Circ_0006168 facilitated Taxol resistance in ESCC by regulating miR-194-5p/JMJD1C axis, providing a promising therapeutic target for ESCC chemotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01984-y. |
format | Online Article Text |
id | pubmed-8141117 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-81411172021-05-25 Circular RNA circ_0006168 enhances Taxol resistance in esophageal squamous cell carcinoma by regulating miR-194-5p/JMJD1C axis Qu, Fanyong Wang, Lina Wang, Caiyan Yu, Lingxia Zhao, Kaikai Zhong, Hao Cancer Cell Int Primary Research BACKGROUND: Chemoresistance is one of the major obstacles for cancer therapy in the clinic. Circular RNAs (circRNAs) are involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and chemoresistance. This study aimed to explore the role and molecular mechanism of circ_0006168 in Taxol resistance of ESCC. METHODS: The expression levels of circ_0006168, microRNA-194-5p (miR-194-5p) and jumonji domain containing 1C (JMJD1C) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The half-inhibition concentration (IC(50)) value of Taxol was evaluated by Cell Counting Kit-8 (CCK-8) assay. Cell proliferation was evaluated by CCK-8 and colony formation assays. Cell migration and invasion were detected by transwell assay. Cell apoptosis was determined by flow cytometry. The interaction between miR-194-5p and circ_0006168 or JMJD1C was predicted by bioinformatics analysis (Circinteractome and TargetScan) and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) and RNA pull-down assays. The mice xenograft model was established to investigate the roles of circ_0006168 in vivo. RESULTS: Circ_0006168 and JMJD1C were upregulated and miR-194-5p was downregulated in ESCC tissues, ESCC cells, and Taxol-resistant cells. Functionally, knockdown of circ_0006168 or JMJD1C increased Taxol sensitivity of ESCC in vitro via inhibiting cell proliferation, migration and invasion, and promoting apoptosis. Moreover, circ_0006168 could directly bind to miR-194-5p and JMJD1C was verified as a direct target of miR-194-5p. Mechanically, circ_0006168 was a sponge of miR-194-5p to regulate JMJD1C expression in ESCC cells. Furthermore, JMJD1C overexpression reversed the promotive effect of circ_0006168 knockdown on Taxol sensitivity. Besides, circ_0006168 silence suppressed tumor growth in vivo. CONCLUSION: Circ_0006168 facilitated Taxol resistance in ESCC by regulating miR-194-5p/JMJD1C axis, providing a promising therapeutic target for ESCC chemotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01984-y. BioMed Central 2021-05-22 /pmc/articles/PMC8141117/ /pubmed/34022910 http://dx.doi.org/10.1186/s12935-021-01984-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Qu, Fanyong Wang, Lina Wang, Caiyan Yu, Lingxia Zhao, Kaikai Zhong, Hao Circular RNA circ_0006168 enhances Taxol resistance in esophageal squamous cell carcinoma by regulating miR-194-5p/JMJD1C axis |
title | Circular RNA circ_0006168 enhances Taxol resistance in esophageal squamous cell carcinoma by regulating miR-194-5p/JMJD1C axis |
title_full | Circular RNA circ_0006168 enhances Taxol resistance in esophageal squamous cell carcinoma by regulating miR-194-5p/JMJD1C axis |
title_fullStr | Circular RNA circ_0006168 enhances Taxol resistance in esophageal squamous cell carcinoma by regulating miR-194-5p/JMJD1C axis |
title_full_unstemmed | Circular RNA circ_0006168 enhances Taxol resistance in esophageal squamous cell carcinoma by regulating miR-194-5p/JMJD1C axis |
title_short | Circular RNA circ_0006168 enhances Taxol resistance in esophageal squamous cell carcinoma by regulating miR-194-5p/JMJD1C axis |
title_sort | circular rna circ_0006168 enhances taxol resistance in esophageal squamous cell carcinoma by regulating mir-194-5p/jmjd1c axis |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141117/ https://www.ncbi.nlm.nih.gov/pubmed/34022910 http://dx.doi.org/10.1186/s12935-021-01984-y |
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