Cargando…

The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas

BACKGROUND: Fenofibrate is a fibric acid derivative known to have a lipid-lowering effect. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcription activation has been shown to play an important role in the malignant progression of gliomas, the underlying m...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Wei, Zhao, Hongyang, Xu, Fenfen, Huang, Bin, Dai, Xiaojing, Sun, Jikui, Nyalali, Alphonce M. K., Zhang, Kailiang, Ni, Shilei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173837/
https://www.ncbi.nlm.nih.gov/pubmed/34082742
http://dx.doi.org/10.1186/s12885-021-08417-z
_version_ 1783702788189978624
author Zhu, Wei
Zhao, Hongyang
Xu, Fenfen
Huang, Bin
Dai, Xiaojing
Sun, Jikui
Nyalali, Alphonce M. K.
Zhang, Kailiang
Ni, Shilei
author_facet Zhu, Wei
Zhao, Hongyang
Xu, Fenfen
Huang, Bin
Dai, Xiaojing
Sun, Jikui
Nyalali, Alphonce M. K.
Zhang, Kailiang
Ni, Shilei
author_sort Zhu, Wei
collection PubMed
description BACKGROUND: Fenofibrate is a fibric acid derivative known to have a lipid-lowering effect. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcription activation has been shown to play an important role in the malignant progression of gliomas, the underlying mechanisms are poorly understood. METHODS: In this study, we analyzed TCGA database and found that there was a significant negative correlation between the long noncoding RNA (lncRNA) HOTAIR and PPARα. Then, we explored the molecular mechanism by which lncRNA HOTAIR regulates PPARα in cell lines in vitro and in a nude mouse glioma model in vivo and explored the effect of the combined application of HOTAIR knockdown and fenofibrate treatment on glioma invasion. RESULTS: For the first time, it was shown that after knockdown of the expression of HOTAIR in gliomas, the expression of PPARα was significantly upregulated, and the invasion and proliferation ability of gliomas were obviously inhibited. Then, glioma cells were treated with both the PPARα agonist fenofibrate and si-HOTAIR, and the results showed that the proliferation and invasion of glioma cells were significantly inhibited. CONCLUSIONS: Our results suggest that HOTAIR can negatively regulate the expression of PPARα and that the combination of fenofibrate and si-HOTAIR treatment can significantly inhibit the progression of gliomas. This introduces new ideas for the treatment of gliomas. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08417-z.
format Online
Article
Text
id pubmed-8173837
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-81738372021-06-03 The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas Zhu, Wei Zhao, Hongyang Xu, Fenfen Huang, Bin Dai, Xiaojing Sun, Jikui Nyalali, Alphonce M. K. Zhang, Kailiang Ni, Shilei BMC Cancer Research BACKGROUND: Fenofibrate is a fibric acid derivative known to have a lipid-lowering effect. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcription activation has been shown to play an important role in the malignant progression of gliomas, the underlying mechanisms are poorly understood. METHODS: In this study, we analyzed TCGA database and found that there was a significant negative correlation between the long noncoding RNA (lncRNA) HOTAIR and PPARα. Then, we explored the molecular mechanism by which lncRNA HOTAIR regulates PPARα in cell lines in vitro and in a nude mouse glioma model in vivo and explored the effect of the combined application of HOTAIR knockdown and fenofibrate treatment on glioma invasion. RESULTS: For the first time, it was shown that after knockdown of the expression of HOTAIR in gliomas, the expression of PPARα was significantly upregulated, and the invasion and proliferation ability of gliomas were obviously inhibited. Then, glioma cells were treated with both the PPARα agonist fenofibrate and si-HOTAIR, and the results showed that the proliferation and invasion of glioma cells were significantly inhibited. CONCLUSIONS: Our results suggest that HOTAIR can negatively regulate the expression of PPARα and that the combination of fenofibrate and si-HOTAIR treatment can significantly inhibit the progression of gliomas. This introduces new ideas for the treatment of gliomas. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08417-z. BioMed Central 2021-06-03 /pmc/articles/PMC8173837/ /pubmed/34082742 http://dx.doi.org/10.1186/s12885-021-08417-z Text en © The Author(s) 2021 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, visit http://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
Zhu, Wei
Zhao, Hongyang
Xu, Fenfen
Huang, Bin
Dai, Xiaojing
Sun, Jikui
Nyalali, Alphonce M. K.
Zhang, Kailiang
Ni, Shilei
The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas
title The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas
title_full The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas
title_fullStr The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas
title_full_unstemmed The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas
title_short The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas
title_sort lipid-lowering drug fenofibrate combined with si-hotair can effectively inhibit the proliferation of gliomas
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173837/
https://www.ncbi.nlm.nih.gov/pubmed/34082742
http://dx.doi.org/10.1186/s12885-021-08417-z
work_keys_str_mv AT zhuwei thelipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT zhaohongyang thelipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT xufenfen thelipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT huangbin thelipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT daixiaojing thelipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT sunjikui thelipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT nyalalialphoncemk thelipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT zhangkailiang thelipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT nishilei thelipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT zhuwei lipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT zhaohongyang lipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT xufenfen lipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT huangbin lipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT daixiaojing lipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT sunjikui lipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT nyalalialphoncemk lipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT zhangkailiang lipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas
AT nishilei lipidloweringdrugfenofibratecombinedwithsihotaircaneffectivelyinhibittheproliferationofgliomas