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Long Noncoding RNA NEAT1 Promotes Cell Proliferation And Invasion And Suppresses Apoptosis In Hepatocellular Carcinoma By Regulating miRNA-22-3p/akt2 In Vitro And In Vivo

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most aggressive cancers that is associated with cirrhosis and other chronic liver diseases. Although remarkable progress has been made in past decades, it is still necessary to continue exploring the pathology and development of HCC. OBJECTIVE...

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Autores principales: Zhou, Xichang, Wang, Xiang, Zhou, Yizhou, Cheng, Long, Zhang, Youwei, Zhang, Yangmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827517/
https://www.ncbi.nlm.nih.gov/pubmed/31802908
http://dx.doi.org/10.2147/OTT.S224521
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author Zhou, Xichang
Wang, Xiang
Zhou, Yizhou
Cheng, Long
Zhang, Youwei
Zhang, Yangmei
author_facet Zhou, Xichang
Wang, Xiang
Zhou, Yizhou
Cheng, Long
Zhang, Youwei
Zhang, Yangmei
author_sort Zhou, Xichang
collection PubMed
description BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most aggressive cancers that is associated with cirrhosis and other chronic liver diseases. Although remarkable progress has been made in past decades, it is still necessary to continue exploring the pathology and development of HCC. OBJECTIVE: In this study, we elucidated the effect of long noncoding RNA (lncRNA) NEAT1 on HCC development and underlying mechanisms. METHODS: Clinicopathological features of HCC patients were collected and the correlations with NEAT1 expression were assessed. To determine cell activities, CCK-8, flow cytometry, invasion assays, and TUNEL assays were performed. Real-time PCR, Western blot, and luciferase reporter assays were performed to investigate the related mechanism of HCC. RESULTS: The results revealed that NEAT1 expression was associated with tumor size and differentiation where NEAT1 was upregulated in both HCC tissues and cell lines. Overexpression of NEAT1 promoted proliferation and invasion while inhibited apoptosis in HCC cells, which was opposite to the effect of NEAT1 knockdown. Also, AKT2 was increased in HCC tissues. Downregulation of AKT2 was associated with reduced cell proliferation and invasion while increased apoptosis, while overexpression of AKT2 exerted opposite roles. In addition, the expression of miRNA-22-3p displayed an inverse association with NEAT1. miRNA-22-3p mimic and inhibitor suppressed and promoted HCC development, respectively. The luciferase assay revealed that both NEAT1 and AKT2 were direct target genes of miRNA-22-3p. Furthermore, knockdown and overexpression of NEAT1 suppressed and promoted tumor growth in the HCC mouse model, which were abolished by the miRNA-22-3p inhibitor and mimic, respectively. CONCLUSION: In conclusion, the results demonstrate that NEAT1 promotes the development of HCC, both in vitro and in vivo, through regulating miRNA-22-3p/AKT2, and provides insight into developing a new strategy for HCC treatment.
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spelling pubmed-68275172019-12-04 Long Noncoding RNA NEAT1 Promotes Cell Proliferation And Invasion And Suppresses Apoptosis In Hepatocellular Carcinoma By Regulating miRNA-22-3p/akt2 In Vitro And In Vivo Zhou, Xichang Wang, Xiang Zhou, Yizhou Cheng, Long Zhang, Youwei Zhang, Yangmei Onco Targets Ther Original Research BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most aggressive cancers that is associated with cirrhosis and other chronic liver diseases. Although remarkable progress has been made in past decades, it is still necessary to continue exploring the pathology and development of HCC. OBJECTIVE: In this study, we elucidated the effect of long noncoding RNA (lncRNA) NEAT1 on HCC development and underlying mechanisms. METHODS: Clinicopathological features of HCC patients were collected and the correlations with NEAT1 expression were assessed. To determine cell activities, CCK-8, flow cytometry, invasion assays, and TUNEL assays were performed. Real-time PCR, Western blot, and luciferase reporter assays were performed to investigate the related mechanism of HCC. RESULTS: The results revealed that NEAT1 expression was associated with tumor size and differentiation where NEAT1 was upregulated in both HCC tissues and cell lines. Overexpression of NEAT1 promoted proliferation and invasion while inhibited apoptosis in HCC cells, which was opposite to the effect of NEAT1 knockdown. Also, AKT2 was increased in HCC tissues. Downregulation of AKT2 was associated with reduced cell proliferation and invasion while increased apoptosis, while overexpression of AKT2 exerted opposite roles. In addition, the expression of miRNA-22-3p displayed an inverse association with NEAT1. miRNA-22-3p mimic and inhibitor suppressed and promoted HCC development, respectively. The luciferase assay revealed that both NEAT1 and AKT2 were direct target genes of miRNA-22-3p. Furthermore, knockdown and overexpression of NEAT1 suppressed and promoted tumor growth in the HCC mouse model, which were abolished by the miRNA-22-3p inhibitor and mimic, respectively. CONCLUSION: In conclusion, the results demonstrate that NEAT1 promotes the development of HCC, both in vitro and in vivo, through regulating miRNA-22-3p/AKT2, and provides insight into developing a new strategy for HCC treatment. Dove 2019-10-31 /pmc/articles/PMC6827517/ /pubmed/31802908 http://dx.doi.org/10.2147/OTT.S224521 Text en © 2019 Zhou 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
Zhou, Xichang
Wang, Xiang
Zhou, Yizhou
Cheng, Long
Zhang, Youwei
Zhang, Yangmei
Long Noncoding RNA NEAT1 Promotes Cell Proliferation And Invasion And Suppresses Apoptosis In Hepatocellular Carcinoma By Regulating miRNA-22-3p/akt2 In Vitro And In Vivo
title Long Noncoding RNA NEAT1 Promotes Cell Proliferation And Invasion And Suppresses Apoptosis In Hepatocellular Carcinoma By Regulating miRNA-22-3p/akt2 In Vitro And In Vivo
title_full Long Noncoding RNA NEAT1 Promotes Cell Proliferation And Invasion And Suppresses Apoptosis In Hepatocellular Carcinoma By Regulating miRNA-22-3p/akt2 In Vitro And In Vivo
title_fullStr Long Noncoding RNA NEAT1 Promotes Cell Proliferation And Invasion And Suppresses Apoptosis In Hepatocellular Carcinoma By Regulating miRNA-22-3p/akt2 In Vitro And In Vivo
title_full_unstemmed Long Noncoding RNA NEAT1 Promotes Cell Proliferation And Invasion And Suppresses Apoptosis In Hepatocellular Carcinoma By Regulating miRNA-22-3p/akt2 In Vitro And In Vivo
title_short Long Noncoding RNA NEAT1 Promotes Cell Proliferation And Invasion And Suppresses Apoptosis In Hepatocellular Carcinoma By Regulating miRNA-22-3p/akt2 In Vitro And In Vivo
title_sort long noncoding rna neat1 promotes cell proliferation and invasion and suppresses apoptosis in hepatocellular carcinoma by regulating mirna-22-3p/akt2 in vitro and in vivo
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827517/
https://www.ncbi.nlm.nih.gov/pubmed/31802908
http://dx.doi.org/10.2147/OTT.S224521
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