Skip to main content
Top
Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Glioblastoma | Research

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

Authors: Wei Zhu, Hongyang Zhao, Fenfen Xu, Bin Huang, Xiaojing Dai, Jikui Sun, Alphonce M. K. Nyalali, Kailiang Zhang, Shilei Ni

Published in: BMC Cancer | Issue 1/2021

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
8.
go back to reference Simula MP, Cannizzaro R, Canzonieri V, Pavan A, Maiero S, Toffoli G, et al. PPAR signaling pathway and cancer-related proteins are involved in celiac disease-associated tissue damage. Mol Med (Cambridge, Mass). 2010;16(5–6):199–209.CrossRef Simula MP, Cannizzaro R, Canzonieri V, Pavan A, Maiero S, Toffoli G, et al. PPAR signaling pathway and cancer-related proteins are involved in celiac disease-associated tissue damage. Mol Med (Cambridge, Mass). 2010;16(5–6):199–209.CrossRef
10.
go back to reference Portius D, Sobolewski C, Foti M. MicroRNAs-dependent regulation of PPARs in metabolic diseases and cancers. PPAR Res. 2017;2017:7058424.CrossRef Portius D, Sobolewski C, Foti M. MicroRNAs-dependent regulation of PPARs in metabolic diseases and cancers. PPAR Res. 2017;2017:7058424.CrossRef
12.
go back to reference Zhang K, Sun X, Zhou X, Han L, Chen L, Shi Z, et al. Long non-coding RNA HOTAIR promotes glioblastoma cell cycle progression in an EZH2 dependent manner. Oncotarget. 2014;6(1):537–46.CrossRef Zhang K, Sun X, Zhou X, Han L, Chen L, Shi Z, et al. Long non-coding RNA HOTAIR promotes glioblastoma cell cycle progression in an EZH2 dependent manner. Oncotarget. 2014;6(1):537–46.CrossRef
15.
go back to reference Cheng CK, Fan Q-W, Weiss WA. PI3K signaling in glioma--animal models and therapeutic challenges. Brain Pathol (Zurich, Switzerland). 2009;19(1):112–20.CrossRef Cheng CK, Fan Q-W, Weiss WA. PI3K signaling in glioma--animal models and therapeutic challenges. Brain Pathol (Zurich, Switzerland). 2009;19(1):112–20.CrossRef
17.
go back to reference Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2019;2019:1. Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2019;2019:1.
Metadata
Title
The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas
Authors
Wei Zhu
Hongyang Zhao
Fenfen Xu
Bin Huang
Xiaojing Dai
Jikui Sun
Alphonce M. K. Nyalali
Kailiang Zhang
Shilei Ni
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-08417-z

Other articles of this Issue 1/2021

BMC Cancer 1/2021 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine