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Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression
BACKGROUND: Cisplatin (CDDP) treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). A better understanding of the mechanisms of CDDP resistance can greatly improve therapeutic efficacy in patients with GC. Circular RNAs (circRNAs) are a class of n...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441201/ https://www.ncbi.nlm.nih.gov/pubmed/30927924 http://dx.doi.org/10.1186/s12943-019-0969-3 |
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author | Huang, Xiaoxu Li, Zheng Zhang, Qiang Wang, Weizhi Li, Bowen Wang, Lu Xu, Zhipeng Zeng, Ailiang Zhang, Xing Zhang, Xuan He, Zhongyuan Li, Qiang Sun, Guangli Wang, Sen Li, Qing Wang, Linjun Zhang, Lu Xu, Hao Xu, Zekuan |
author_facet | Huang, Xiaoxu Li, Zheng Zhang, Qiang Wang, Weizhi Li, Bowen Wang, Lu Xu, Zhipeng Zeng, Ailiang Zhang, Xing Zhang, Xuan He, Zhongyuan Li, Qiang Sun, Guangli Wang, Sen Li, Qing Wang, Linjun Zhang, Lu Xu, Hao Xu, Zekuan |
author_sort | Huang, Xiaoxu |
collection | PubMed |
description | BACKGROUND: Cisplatin (CDDP) treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). A better understanding of the mechanisms of CDDP resistance can greatly improve therapeutic efficacy in patients with GC. Circular RNAs (circRNAs) are a class of noncoding RNAs whose functions are related to the pathogenesis of cancer, but, in CDDP resistance of GC remains unknown. METHODS: circAKT3 (hsa_circ_0000199, a circRNA originating from exons 8, 9, 10, and 11 of the AKT3 gene) was identified by RNA sequencing and verified by quantitative reverse transcription PCR. The role of circAKT3 in CDDP resistance in GC was assessed both in vitro and in vivo. Luciferase reporter assay, biotin-coupled RNA pull-down and fluorescence in situ hybridization (FISH) were conducted to evaluate the interaction between circAKT3 and miR-198. Functional experiments were measured by western blotting, a cytotoxicity assay, clonogenic assay and flow cytometry. RESULTS: The expression of circAKT3 was higher in CDDP-resistant GC tissues and cells than in CDDP-sensitive samples. The upregulation of circAKT3 in GC patients receiving CDDP therapy was significantly associated with aggressive characteristics and was an independent risk factor for disease-free survival (DFS). Our data indicated that circAKT3 promotes DNA damage repair and inhibits the apoptosis of GC cells in vivo and in vitro. Mechanistically, we verified that circAKT3 could promote PIK3R1 expression by sponging miR-198. CONCLUSIONS: circAKT3 plays an important role in the resistance of GC to CDDP. Thus, our results highlight the potential of circAKT3 as a therapeutic target for GC patients receiving CDDP therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12943-019-0969-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6441201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-64412012019-04-11 Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression Huang, Xiaoxu Li, Zheng Zhang, Qiang Wang, Weizhi Li, Bowen Wang, Lu Xu, Zhipeng Zeng, Ailiang Zhang, Xing Zhang, Xuan He, Zhongyuan Li, Qiang Sun, Guangli Wang, Sen Li, Qing Wang, Linjun Zhang, Lu Xu, Hao Xu, Zekuan Mol Cancer Research BACKGROUND: Cisplatin (CDDP) treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). A better understanding of the mechanisms of CDDP resistance can greatly improve therapeutic efficacy in patients with GC. Circular RNAs (circRNAs) are a class of noncoding RNAs whose functions are related to the pathogenesis of cancer, but, in CDDP resistance of GC remains unknown. METHODS: circAKT3 (hsa_circ_0000199, a circRNA originating from exons 8, 9, 10, and 11 of the AKT3 gene) was identified by RNA sequencing and verified by quantitative reverse transcription PCR. The role of circAKT3 in CDDP resistance in GC was assessed both in vitro and in vivo. Luciferase reporter assay, biotin-coupled RNA pull-down and fluorescence in situ hybridization (FISH) were conducted to evaluate the interaction between circAKT3 and miR-198. Functional experiments were measured by western blotting, a cytotoxicity assay, clonogenic assay and flow cytometry. RESULTS: The expression of circAKT3 was higher in CDDP-resistant GC tissues and cells than in CDDP-sensitive samples. The upregulation of circAKT3 in GC patients receiving CDDP therapy was significantly associated with aggressive characteristics and was an independent risk factor for disease-free survival (DFS). Our data indicated that circAKT3 promotes DNA damage repair and inhibits the apoptosis of GC cells in vivo and in vitro. Mechanistically, we verified that circAKT3 could promote PIK3R1 expression by sponging miR-198. CONCLUSIONS: circAKT3 plays an important role in the resistance of GC to CDDP. Thus, our results highlight the potential of circAKT3 as a therapeutic target for GC patients receiving CDDP therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12943-019-0969-3) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-30 /pmc/articles/PMC6441201/ /pubmed/30927924 http://dx.doi.org/10.1186/s12943-019-0969-3 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Huang, Xiaoxu Li, Zheng Zhang, Qiang Wang, Weizhi Li, Bowen Wang, Lu Xu, Zhipeng Zeng, Ailiang Zhang, Xing Zhang, Xuan He, Zhongyuan Li, Qiang Sun, Guangli Wang, Sen Li, Qing Wang, Linjun Zhang, Lu Xu, Hao Xu, Zekuan Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression |
title | Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression |
title_full | Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression |
title_fullStr | Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression |
title_full_unstemmed | Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression |
title_short | Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression |
title_sort | circular rna akt3 upregulates pik3r1 to enhance cisplatin resistance in gastric cancer via mir-198 suppression |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441201/ https://www.ncbi.nlm.nih.gov/pubmed/30927924 http://dx.doi.org/10.1186/s12943-019-0969-3 |
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