Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 24, Issue 5, Pages 2847-2856Publisher
WILEY
DOI: 10.1111/jcmm.14840
Keywords
apoptosis; autophagy; ER stress; glioblastoma; proteolipid protein 2
Categories
Funding
- Department of Science AMP
- Technology of Shandong Province [2017CXGC1502, 2017CXGC1504, 2018GSF118082]
- National Natural Science Foundation of China [81701329, 81702474]
- Jinan Science and Technology Bureau of Shandong Province [201704096]
- Special Foundation for Taishan Scholars [ts20110814, tshw201502056, tsqn20161067]
- China Postdoctoral Science Foundation [2018M642666]
- Shandong Provincial Natural Science Foundation [ZR2017MH116, ZR2017MH015]
- Stiftelsen Kristian Gerhard Jebsen
- Helse-Vest
- Haukeland Hospital
- University of Bergen
- Norwegian Cancer Society
- Norwegian Research Council
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Proteolipid protein 2 (PLP2) is an integral ion channel membrane protein of the endoplasmic reticulum. The protein has been shown to be highly expressed in many cancer types, but its importance in glioma progression is poorly understood. Using publicly available datasets (Rembrandt, TCGA and CGGA), we found that the expression of PLP2 was significantly higher in high-grade gliomas than in low-grade gliomas. We confirmed these results at the protein level through IHC staining of high-grade (n = 56) and low-grade glioma biopsies (n = 16). Kaplan-Meier analysis demonstrated that increased PLP2 expression was associated with poorer patient survival. In functional experiments, siRNA and shRNA PLP2 knockdown induced ER stress and increased apoptosis and autophagy in U87 and U251 glioma cell lines. Inhibition of autophagy with chloroquine augmented apoptotic cell death in U87- and U251-siPLP2 cells. Finally, intracranial xenografts derived from U87- and U251-shPLP2 cells revealed that loss of PLP2 reduced glioma growth in vivo. Our results therefore indicate that increased PLP2 expression promotes GBM growth and that PLP2 represents a potential future therapeutic target.
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