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MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis
BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy. Long non-coding RNAs (lncRNAs) partake in the progression of HCC. However, the role of lncRNA MAPKAPK5-AS1 in the development of HCC has not been fully clarified. METHODS: RNA sequencing data and quantitative real-time polymerase cha...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036786/ https://www.ncbi.nlm.nih.gov/pubmed/35468721 http://dx.doi.org/10.1186/s12860-022-00420-x |
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author | Peng, Zongqing Ouyang, Xinhua Wang, Yexing Fan, Qiming |
author_facet | Peng, Zongqing Ouyang, Xinhua Wang, Yexing Fan, Qiming |
author_sort | Peng, Zongqing |
collection | PubMed |
description | BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy. Long non-coding RNAs (lncRNAs) partake in the progression of HCC. However, the role of lncRNA MAPKAPK5-AS1 in the development of HCC has not been fully clarified. METHODS: RNA sequencing data and quantitative real-time polymerase chain reaction (qRT-PCR) were adopted to analyze MAPKAPK5-AS1, miR-429 and ZEB1 mRNA expressions in HCC tissues and cell lines. Western blot was used to detect ZEB1, E-cadherin and N-cadherin protein expressions. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell and flow cytometry assays were adopted to analyze the effects of MAPKAPK5-AS1 on cell proliferation, migration, invasion and apoptosis. Besides, luciferase reporter assay was used to detect the targeting relationship between miR-429 and MAPKAPK5-AS1 or ZEB1 3’UTR. The xenograft tumor mouse models were used to explore the effect of MAPKAPK5-AS1 on lung metastasis of HCC cells. RESULTS: MAPKAPK5-AS1 and ZEB1 expressions were up-regulated in HCC tissues, and miR-429 expression is down-regulated in HCC tissues. MAPKAPK5-AS1 knockdown could significantly impede HCC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), as well as promote cell apoptosis. MAPKAPK5-AS1 overexpression could enhance L02 cell proliferation, migration, invasion and EMT, and inhibit cell apoptosis. MiR-429 was validated to be the target of MAPKAPK5-AS1, and miR-429 inhibitors could partially offset the effects of knocking down MAPKAPK5-AS1 on HCC cells. MAPKAPK5-AS1 could positively regulate ZEB1 expression through repressing miR-429. Moreover, fewer lung metastatic nodules were observed in the lung tissues of nude mice when the MAPKAPK5-AS1 was knocked down in HCC cells. CONCLUSION: MAPKAPK5-AS1 can adsorb miR-429 to promote ZEB1 expression to participate in the development of HCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12860-022-00420-x. |
format | Online Article Text |
id | pubmed-9036786 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-90367862022-04-26 MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis Peng, Zongqing Ouyang, Xinhua Wang, Yexing Fan, Qiming BMC Mol Cell Biol Research BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy. Long non-coding RNAs (lncRNAs) partake in the progression of HCC. However, the role of lncRNA MAPKAPK5-AS1 in the development of HCC has not been fully clarified. METHODS: RNA sequencing data and quantitative real-time polymerase chain reaction (qRT-PCR) were adopted to analyze MAPKAPK5-AS1, miR-429 and ZEB1 mRNA expressions in HCC tissues and cell lines. Western blot was used to detect ZEB1, E-cadherin and N-cadherin protein expressions. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell and flow cytometry assays were adopted to analyze the effects of MAPKAPK5-AS1 on cell proliferation, migration, invasion and apoptosis. Besides, luciferase reporter assay was used to detect the targeting relationship between miR-429 and MAPKAPK5-AS1 or ZEB1 3’UTR. The xenograft tumor mouse models were used to explore the effect of MAPKAPK5-AS1 on lung metastasis of HCC cells. RESULTS: MAPKAPK5-AS1 and ZEB1 expressions were up-regulated in HCC tissues, and miR-429 expression is down-regulated in HCC tissues. MAPKAPK5-AS1 knockdown could significantly impede HCC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), as well as promote cell apoptosis. MAPKAPK5-AS1 overexpression could enhance L02 cell proliferation, migration, invasion and EMT, and inhibit cell apoptosis. MiR-429 was validated to be the target of MAPKAPK5-AS1, and miR-429 inhibitors could partially offset the effects of knocking down MAPKAPK5-AS1 on HCC cells. MAPKAPK5-AS1 could positively regulate ZEB1 expression through repressing miR-429. Moreover, fewer lung metastatic nodules were observed in the lung tissues of nude mice when the MAPKAPK5-AS1 was knocked down in HCC cells. CONCLUSION: MAPKAPK5-AS1 can adsorb miR-429 to promote ZEB1 expression to participate in the development of HCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12860-022-00420-x. BioMed Central 2022-04-25 /pmc/articles/PMC9036786/ /pubmed/35468721 http://dx.doi.org/10.1186/s12860-022-00420-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visithttp://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Peng, Zongqing Ouyang, Xinhua Wang, Yexing Fan, Qiming MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis |
title | MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis |
title_full | MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis |
title_fullStr | MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis |
title_full_unstemmed | MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis |
title_short | MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis |
title_sort | mapkapk5-as1 drives the progression of hepatocellular carcinoma via regulating mir-429/zeb1 axis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036786/ https://www.ncbi.nlm.nih.gov/pubmed/35468721 http://dx.doi.org/10.1186/s12860-022-00420-x |
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