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Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A
Background: Gastric cancer (GC) remains one of the most common malignancies worldwide. Increasing evidence has demonstrated that circRNAs serve as critical roles in human cancer, including GC. In the present study, we focused on the detailed function and mechanism of circ_0000144 on GC progression....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426631/ https://www.ncbi.nlm.nih.gov/pubmed/32766708 http://dx.doi.org/10.1042/BSR20201313 |
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author | Mi, Lili Lei, Lianhui Yin, Xiaolei Li, Ning Shi, Jianfei Han, Xin Duan, Xiaoling Zhao, Man Han, Guangjie Wang, Jinfeng Yin, Fei |
author_facet | Mi, Lili Lei, Lianhui Yin, Xiaolei Li, Ning Shi, Jianfei Han, Xin Duan, Xiaoling Zhao, Man Han, Guangjie Wang, Jinfeng Yin, Fei |
author_sort | Mi, Lili |
collection | PubMed |
description | Background: Gastric cancer (GC) remains one of the most common malignancies worldwide. Increasing evidence has demonstrated that circRNAs serve as critical roles in human cancer, including GC. In the present study, we focused on the detailed function and mechanism of circ_0000144 on GC progression. Methods: The levels of circ_0000144, miR-623 and G-protein-coupled receptor, family C, group 5, member A (GPRC5A) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Targeted relationships among circ_0000144, miR-623 and GPRC5A were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, colony formation, apoptosis, migration and invasion were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry and transwell assays. Measurement of glutamine and α-ketoglutarate (α-KG) levels was performed using a corresponding assay kit. GPRC5A protein expression was detected using Western blot. In vivo assays were used to explore the impact of circ_0000144 on tumor growth. Results: Our data indicated that circ_0000144 was up-regulated and miR-623 was down-regulated in GC tissues and cells. Circ_0000144 interacted with miR-623 through directly binding to miR-623. Moreover, the knockdown of circ_0000144 weakened GC cell proliferation, colony formation, migration, invasion and glutaminolysis and accelerated cell apoptosis by up-regulating miR-623. GPRC5A was a direct target of miR-623 and circ_0000144 protected against GPRC5A repression through sponging miR-623. Furthermore, miR-623-mediated regulation on GC cell progression was reversed by the stored expression of GPRC5A. Additionally, circ_0000144 depletion inhibited tumor growth in vivo. Conclusion: Our study indicated that circ-0000144 knockdown repressed GC progression at least partly by regulating GPRC5A expression via sponging miR-623, illumining a novel therapeutic target for GC treatment. |
format | Online Article Text |
id | pubmed-7426631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74266312020-08-20 Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A Mi, Lili Lei, Lianhui Yin, Xiaolei Li, Ning Shi, Jianfei Han, Xin Duan, Xiaoling Zhao, Man Han, Guangjie Wang, Jinfeng Yin, Fei Biosci Rep Cancer Background: Gastric cancer (GC) remains one of the most common malignancies worldwide. Increasing evidence has demonstrated that circRNAs serve as critical roles in human cancer, including GC. In the present study, we focused on the detailed function and mechanism of circ_0000144 on GC progression. Methods: The levels of circ_0000144, miR-623 and G-protein-coupled receptor, family C, group 5, member A (GPRC5A) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Targeted relationships among circ_0000144, miR-623 and GPRC5A were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, colony formation, apoptosis, migration and invasion were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry and transwell assays. Measurement of glutamine and α-ketoglutarate (α-KG) levels was performed using a corresponding assay kit. GPRC5A protein expression was detected using Western blot. In vivo assays were used to explore the impact of circ_0000144 on tumor growth. Results: Our data indicated that circ_0000144 was up-regulated and miR-623 was down-regulated in GC tissues and cells. Circ_0000144 interacted with miR-623 through directly binding to miR-623. Moreover, the knockdown of circ_0000144 weakened GC cell proliferation, colony formation, migration, invasion and glutaminolysis and accelerated cell apoptosis by up-regulating miR-623. GPRC5A was a direct target of miR-623 and circ_0000144 protected against GPRC5A repression through sponging miR-623. Furthermore, miR-623-mediated regulation on GC cell progression was reversed by the stored expression of GPRC5A. Additionally, circ_0000144 depletion inhibited tumor growth in vivo. Conclusion: Our study indicated that circ-0000144 knockdown repressed GC progression at least partly by regulating GPRC5A expression via sponging miR-623, illumining a novel therapeutic target for GC treatment. Portland Press Ltd. 2020-08-13 /pmc/articles/PMC7426631/ /pubmed/32766708 http://dx.doi.org/10.1042/BSR20201313 Text en © 2020 The Author(s). https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). |
spellingShingle | Cancer Mi, Lili Lei, Lianhui Yin, Xiaolei Li, Ning Shi, Jianfei Han, Xin Duan, Xiaoling Zhao, Man Han, Guangjie Wang, Jinfeng Yin, Fei Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A |
title | Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A |
title_full | Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A |
title_fullStr | Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A |
title_full_unstemmed | Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A |
title_short | Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A |
title_sort | circ_0000144 functions as a mir-623 sponge to enhance gastric cancer progression via up-regulating gprc5a |
topic | Cancer |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426631/ https://www.ncbi.nlm.nih.gov/pubmed/32766708 http://dx.doi.org/10.1042/BSR20201313 |
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