Piwil1 Regulates Glioma Stem Cell Maintenance and Glioblastoma Progression
Haidong Huang1, Xingjiang Yu1, Xiangzi Han1
1Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, NE60, Cleveland, OH 44195, USA.
Cell Reports
|January 6, 2021
Summary
Piwi-like protein 1 (Piwil1) is overexpressed in glioblastoma and maintains cancer stem cell self-renewal. Silencing Piwil1 inhibits tumor growth and improves survival in glioblastoma models.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Piwi proteins are crucial for germ cell maintenance in eukaryotes.
- The function of human Piwi homologs in cancer stem cells, particularly glioblastoma, remains largely unexplored.
Purpose of the Study:
- To investigate the role of Piwi-like proteins in glioblastoma (GBM) and glioma stem-like cells (GSCs).
- To determine the impact of Piwil1 (Hiwi) on GSC self-renewal and GBM progression.
Main Methods:
- Quantitative analysis of Piwi-like family member expression in GBM.
- Functional studies involving Piwil1 knockdown in GSCs.
- Gene expression profiling and mRNA stability assays.
- In vivo assessment of Piwil1's role in GBM animal models.
Main Results:
- Piwi-like proteins, especially Piwil1 (Hiwi), are frequently overexpressed in glioblastoma (88%).
- Piwil1 is essential for maintaining self-renewal in glioma stem-like cells.
- Piwil1 knockdown induces cell-cycle arrest, senescence, or apoptosis, reduces c-Myc, and affects stem cell factors (Olig2, Nestin).
- Piwil1 regulates the mRNA stability of BTG2, FBXW7, and CDKN1B.
- Piwil1 inhibition suppresses tumor growth and enhances survival in GBM animal models.
Conclusions:
- Piwil1 plays a critical role in the maintenance of glioma stem-like cells.
- Piwil1 is a key driver of glioblastoma progression and a potential therapeutic target.
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