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P4HA1 Down-Regulation Inhibits Glioma Invasiveness by Promoting M1 Microglia Polarization

Authors Wang Q, Zhang J, Fang S, Wang J, Han X, Liu F, Jin G

Received 31 December 2020

Accepted for publication 16 February 2021

Published 8 March 2021 Volume 2021:14 Pages 1771—1782

DOI https://doi.org/10.2147/OTT.S299977

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr William Cho


Qiyan Wang,* Junwen Zhang,* Sheng Fang, Jialin Wang, Xiangming Han, Fusheng Liu, Guishan Jin

Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Laboratory of Biomedical Materials, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, 10070, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Guishan Jin; Fusheng Liu
Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Laboratory of Biomedical Materials, Beijing Tiantan Hospital Affiliated to Capital Medical University, No. 119 Nansihuanxilu, Fengtai District, Beijing, 100070, People’s Republic of China
Tel +86-10-59975626
Email [email protected]; [email protected]

Background: Polarization of microglia cells in the glioma microenvironment is closely related to the malignant progression and invasion of gliomas. Prolyl 4-hydroxylase subunit α 1 (P4HA1) is the rate-limiting subunit of prolyl 4-hydroxylase (P4H). In previous studies, we showed that P4HA1 could promote the proliferation, migration, and invasion of glioma cells, but the specific mechanisms through which this occurs have not been fully elucidated.
Materials and Methods: Interactions between glioma and microglia cells were analyzed using bioinformatics. Then, co-culture models were used to obtain conditioned media. To characterize microglial cell polarization, we used PCR and immunofluorescence. Proliferation and invasion assays were used to explore the biological behavior of glioma cells affected by microglia. Finally, marker expression was detected using immunohistochemistry in glioblastoma multiform (GBM) specimens.
Results: Knockdown of P4HA1 resulted in reduced chemotaxis of microglia toward GBM cells and increased polarization of microglia toward the M1 phenotype. The changed microglial polarization state, in turn, inhibited the proliferation and invasion of GBM cells. Moreover, in GBM tissue specimens, the P4HA1 expression level is negatively correlated with that of the CD86 microglia M1-specific marker.
Conclusion: Our results show that P4HA1 promotes immunosuppressive microenvironment formation by cross-talk between GBM and microglia cells and indirectly increases the aggressiveness of GBM.

Keywords: glioma, microglia, P4HA1, polarization, invasiveness

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