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Circ_0058124 Upregulates MAPK1 Expression to Promote Proliferation, Metastasis and Metabolic Abilities in Thyroid Cancer Through Sponging miR-940

BACKGROUND: Thyroid cancer (TC) is an endocrine disease, and its progression is regulated by many factors, including circular RNAs (circRNAs). However, as a new circRNA, the role of circ_0058124 in TC is worth further exploration. METHODS: The expression levels of circ_0058124, microRNA-940 (miR-940...

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Autores principales: Sun, Dezhong, Chen, Li, Lv, Huaiqing, Gao, Yongli, Liu, Xuelai, Zhang, Xiaoyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037104/
https://www.ncbi.nlm.nih.gov/pubmed/32110054
http://dx.doi.org/10.2147/OTT.S237307
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author Sun, Dezhong
Chen, Li
Lv, Huaiqing
Gao, Yongli
Liu, Xuelai
Zhang, Xiaoyan
author_facet Sun, Dezhong
Chen, Li
Lv, Huaiqing
Gao, Yongli
Liu, Xuelai
Zhang, Xiaoyan
author_sort Sun, Dezhong
collection PubMed
description BACKGROUND: Thyroid cancer (TC) is an endocrine disease, and its progression is regulated by many factors, including circular RNAs (circRNAs). However, as a new circRNA, the role of circ_0058124 in TC is worth further exploration. METHODS: The expression levels of circ_0058124, microRNA-940 (miR-940) and mitogen-activated protein kinase 1 (MAPK1) were assessed by quantitative polymerase chain reaction (q-PCR). The circular characteristic of circ_0058124 was identified by oligo (dT)(18) primers, Ribonuclease R (RNase R) and Actinomycin D (ActD), and its localization was determined by nuclear-cytoplasmic separation assay. Also, cell proliferation was detected by colony formation assay, and cell migration and invasion were assessed by transwell assay. Further, Seahorse XF Extracellular Flux Analyzer was used to measure the oxygen consumption rate (OCR) of cells. Besides, dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were used to identify the mechanism of circ_0058124. Western blot (WB) analysis was used to test the MAPK1 protein level. In addition, mice xenograft models were constructed to test the effect of circ_0058124 on TC tumor growth in vivo. RESULTS: Circ_0058124 was highly expressed in TC and is a stable cyclic transcript, mainly located in the cytoplasm. Circ_0058124 knockdown suppressed proliferation, migration, invasion and metabolic abilities in TC cells. MiR-940 could be absorbed by circ_0058124, and the inhibition effect of its overexpression on TC progression could be reversed by overexpressed-circ_0058124. MAPK1 was a target of miR-940, and the suppression effect of its silencing on TC progression could be inverted by miR-940 inhibitor. Besides, MAPK1 expression was regulated by circ_0058124 and miR-940. Interference of circ_0058124 also reduced TC tumor growth in vivo. CONCLUSION: Circ_0058124 might play a carcinogenic role in TC progression by regulating the miR-940/MAPK1 axis, which might provide a new idea for the treatment of TC.
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spelling pubmed-70371042020-02-27 Circ_0058124 Upregulates MAPK1 Expression to Promote Proliferation, Metastasis and Metabolic Abilities in Thyroid Cancer Through Sponging miR-940 Sun, Dezhong Chen, Li Lv, Huaiqing Gao, Yongli Liu, Xuelai Zhang, Xiaoyan Onco Targets Ther Original Research BACKGROUND: Thyroid cancer (TC) is an endocrine disease, and its progression is regulated by many factors, including circular RNAs (circRNAs). However, as a new circRNA, the role of circ_0058124 in TC is worth further exploration. METHODS: The expression levels of circ_0058124, microRNA-940 (miR-940) and mitogen-activated protein kinase 1 (MAPK1) were assessed by quantitative polymerase chain reaction (q-PCR). The circular characteristic of circ_0058124 was identified by oligo (dT)(18) primers, Ribonuclease R (RNase R) and Actinomycin D (ActD), and its localization was determined by nuclear-cytoplasmic separation assay. Also, cell proliferation was detected by colony formation assay, and cell migration and invasion were assessed by transwell assay. Further, Seahorse XF Extracellular Flux Analyzer was used to measure the oxygen consumption rate (OCR) of cells. Besides, dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were used to identify the mechanism of circ_0058124. Western blot (WB) analysis was used to test the MAPK1 protein level. In addition, mice xenograft models were constructed to test the effect of circ_0058124 on TC tumor growth in vivo. RESULTS: Circ_0058124 was highly expressed in TC and is a stable cyclic transcript, mainly located in the cytoplasm. Circ_0058124 knockdown suppressed proliferation, migration, invasion and metabolic abilities in TC cells. MiR-940 could be absorbed by circ_0058124, and the inhibition effect of its overexpression on TC progression could be reversed by overexpressed-circ_0058124. MAPK1 was a target of miR-940, and the suppression effect of its silencing on TC progression could be inverted by miR-940 inhibitor. Besides, MAPK1 expression was regulated by circ_0058124 and miR-940. Interference of circ_0058124 also reduced TC tumor growth in vivo. CONCLUSION: Circ_0058124 might play a carcinogenic role in TC progression by regulating the miR-940/MAPK1 axis, which might provide a new idea for the treatment of TC. Dove 2020-02-19 /pmc/articles/PMC7037104/ /pubmed/32110054 http://dx.doi.org/10.2147/OTT.S237307 Text en © 2020 Sun 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
Sun, Dezhong
Chen, Li
Lv, Huaiqing
Gao, Yongli
Liu, Xuelai
Zhang, Xiaoyan
Circ_0058124 Upregulates MAPK1 Expression to Promote Proliferation, Metastasis and Metabolic Abilities in Thyroid Cancer Through Sponging miR-940
title Circ_0058124 Upregulates MAPK1 Expression to Promote Proliferation, Metastasis and Metabolic Abilities in Thyroid Cancer Through Sponging miR-940
title_full Circ_0058124 Upregulates MAPK1 Expression to Promote Proliferation, Metastasis and Metabolic Abilities in Thyroid Cancer Through Sponging miR-940
title_fullStr Circ_0058124 Upregulates MAPK1 Expression to Promote Proliferation, Metastasis and Metabolic Abilities in Thyroid Cancer Through Sponging miR-940
title_full_unstemmed Circ_0058124 Upregulates MAPK1 Expression to Promote Proliferation, Metastasis and Metabolic Abilities in Thyroid Cancer Through Sponging miR-940
title_short Circ_0058124 Upregulates MAPK1 Expression to Promote Proliferation, Metastasis and Metabolic Abilities in Thyroid Cancer Through Sponging miR-940
title_sort circ_0058124 upregulates mapk1 expression to promote proliferation, metastasis and metabolic abilities in thyroid cancer through sponging mir-940
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037104/
https://www.ncbi.nlm.nih.gov/pubmed/32110054
http://dx.doi.org/10.2147/OTT.S237307
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