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Circ_0007031 Serves as a Sponge of miR-760 to Regulate the Growth and Chemoradiotherapy Resistance of Colorectal Cancer via Regulating DCP1A
BACKGROUND: Colorectal cancer (CRC) is a kind of malignant tumor, and the development of chemoradiotherapy resistance (CRR) increases the difficulty of its treatment. The role of circular RNAs (circRNAs) in cancer progression has been well documented. Nevertheless, the function of circ_0007031 in th...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500843/ https://www.ncbi.nlm.nih.gov/pubmed/32982440 http://dx.doi.org/10.2147/CMAR.S254815 |
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author | Wang, Yuanyuan Wang, Hua Zhang, Jian Chu, Zhifen Liu, Pu Zhang, Xing Li, Chao Gu, Xiaosong |
author_facet | Wang, Yuanyuan Wang, Hua Zhang, Jian Chu, Zhifen Liu, Pu Zhang, Xing Li, Chao Gu, Xiaosong |
author_sort | Wang, Yuanyuan |
collection | PubMed |
description | BACKGROUND: Colorectal cancer (CRC) is a kind of malignant tumor, and the development of chemoradiotherapy resistance (CRR) increases the difficulty of its treatment. The role of circular RNAs (circRNAs) in cancer progression has been well documented. Nevertheless, the function of circ_0007031 in the growth and CRR of CRC has not been well elucidated. METHODS: CRR cell lines were constructed using 5-Fu and radiation. Cell counting kit 8 (CCK8) assay was employed to measure the 5-Fu resistance and proliferation of cells. Clonogenic assay was used to evaluate the radiation resistance of cells. Also, the expression of circ_0007031 and microRNA-760 (miR-760) was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle distribution and apoptosis of cells were assessed by flow cytometry. Besides, the levels of apoptosis-related protein and mRNA-decapping enzyme 1a (DCP1A) protein were measured by Western blot (WB) analysis. Further, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to confirm the interaction between miR-760 and circ_0007031 or DCP1A. In addition, animal experiments were performed to evaluate the function of silenced circ_0007031 on the 5-Fu and radiation resistance of CRC tumors. RESULTS: Circ_0007031 expression was markedly increased in CRC tissues and cells, especially in CRC resistant cells. Circ_0007031 knockdown hindered proliferation, induced cell cycle arrest in the G0/G1 phase, enhanced apoptosis, and lowered the CRR of CRC resistant cells. Further, miR-760 could be targeted by circ_0007031, and its inhibitor could reverse the inhibition effect of circ_0007031 knockdown on the growth and CRR of CRC resistant cells. Moreover, DCP1A was a target of miR-760, and its overexpression could invert the suppression effect of miR-760 overexpression on the growth and CRR of CRC resistant cells. Circ_0007031 silencing could enhance the sensitivity of CRC tumors to 5-Fu and radiation to markedly reduce CRC tumor growth in vivo. CONCLUSION: Circ_0007031 might play a positive role in the CRR of CRC through regulating the miR-760/DCP1A axis, which might provide a new approach for treating the CRR of CRC. |
format | Online Article Text |
id | pubmed-7500843 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-75008432020-09-24 Circ_0007031 Serves as a Sponge of miR-760 to Regulate the Growth and Chemoradiotherapy Resistance of Colorectal Cancer via Regulating DCP1A Wang, Yuanyuan Wang, Hua Zhang, Jian Chu, Zhifen Liu, Pu Zhang, Xing Li, Chao Gu, Xiaosong Cancer Manag Res Original Research BACKGROUND: Colorectal cancer (CRC) is a kind of malignant tumor, and the development of chemoradiotherapy resistance (CRR) increases the difficulty of its treatment. The role of circular RNAs (circRNAs) in cancer progression has been well documented. Nevertheless, the function of circ_0007031 in the growth and CRR of CRC has not been well elucidated. METHODS: CRR cell lines were constructed using 5-Fu and radiation. Cell counting kit 8 (CCK8) assay was employed to measure the 5-Fu resistance and proliferation of cells. Clonogenic assay was used to evaluate the radiation resistance of cells. Also, the expression of circ_0007031 and microRNA-760 (miR-760) was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle distribution and apoptosis of cells were assessed by flow cytometry. Besides, the levels of apoptosis-related protein and mRNA-decapping enzyme 1a (DCP1A) protein were measured by Western blot (WB) analysis. Further, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to confirm the interaction between miR-760 and circ_0007031 or DCP1A. In addition, animal experiments were performed to evaluate the function of silenced circ_0007031 on the 5-Fu and radiation resistance of CRC tumors. RESULTS: Circ_0007031 expression was markedly increased in CRC tissues and cells, especially in CRC resistant cells. Circ_0007031 knockdown hindered proliferation, induced cell cycle arrest in the G0/G1 phase, enhanced apoptosis, and lowered the CRR of CRC resistant cells. Further, miR-760 could be targeted by circ_0007031, and its inhibitor could reverse the inhibition effect of circ_0007031 knockdown on the growth and CRR of CRC resistant cells. Moreover, DCP1A was a target of miR-760, and its overexpression could invert the suppression effect of miR-760 overexpression on the growth and CRR of CRC resistant cells. Circ_0007031 silencing could enhance the sensitivity of CRC tumors to 5-Fu and radiation to markedly reduce CRC tumor growth in vivo. CONCLUSION: Circ_0007031 might play a positive role in the CRR of CRC through regulating the miR-760/DCP1A axis, which might provide a new approach for treating the CRR of CRC. Dove 2020-09-14 /pmc/articles/PMC7500843/ /pubmed/32982440 http://dx.doi.org/10.2147/CMAR.S254815 Text en © 2020 Wang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Wang, Yuanyuan Wang, Hua Zhang, Jian Chu, Zhifen Liu, Pu Zhang, Xing Li, Chao Gu, Xiaosong Circ_0007031 Serves as a Sponge of miR-760 to Regulate the Growth and Chemoradiotherapy Resistance of Colorectal Cancer via Regulating DCP1A |
title | Circ_0007031 Serves as a Sponge of miR-760 to Regulate the Growth and Chemoradiotherapy Resistance of Colorectal Cancer via Regulating DCP1A |
title_full | Circ_0007031 Serves as a Sponge of miR-760 to Regulate the Growth and Chemoradiotherapy Resistance of Colorectal Cancer via Regulating DCP1A |
title_fullStr | Circ_0007031 Serves as a Sponge of miR-760 to Regulate the Growth and Chemoradiotherapy Resistance of Colorectal Cancer via Regulating DCP1A |
title_full_unstemmed | Circ_0007031 Serves as a Sponge of miR-760 to Regulate the Growth and Chemoradiotherapy Resistance of Colorectal Cancer via Regulating DCP1A |
title_short | Circ_0007031 Serves as a Sponge of miR-760 to Regulate the Growth and Chemoradiotherapy Resistance of Colorectal Cancer via Regulating DCP1A |
title_sort | circ_0007031 serves as a sponge of mir-760 to regulate the growth and chemoradiotherapy resistance of colorectal cancer via regulating dcp1a |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500843/ https://www.ncbi.nlm.nih.gov/pubmed/32982440 http://dx.doi.org/10.2147/CMAR.S254815 |
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