Abstract
Glioblastoma (GBM), a predominant central nervous system (CNS) malignancy, is correlated with high mortality and severe morbidity. Mammalian methyltransferase-like 7B (METTL7B) as a methyltransferase has been identified to participate in cancer progression. However, its function in GBM is elusive. Accordingly, we aimed to explore the effect of METTL7B on GBM. The expression of METTL7B and EGR2 in GBM patients and GBM cells were detected by qPCR, western blots and immunohistochemical staining. Cell viability was assessed by CCK-8 assays. Cell proliferation was determined by EdU, colony formation, and tumor sphere formation assays. METTL7B shRNA was injected into the Balb/c nude mice. The size and weight of isolated tumor was measured. And the expression levels of Ki67, METTL7B and EGR1 were examined by immunohistochemical staining. METTL7B was significantly elevated, while EGR1 was downregulated in clinical GBM tissues. METTL7B upregulation was associated with the low overall survival of GBM patients. Moreover, METTL7B depletion remarkably attenuated GBM cell proliferation. Mechanistically, METTL7B overexpression inhibited EGR1 expression in GBM cells. EGR1 knockdown rescued the inhibitory effect of METTL7B depletion on GBM cell proliferation. Meanwhile, METTL7B depletion arrested more GBM cells at the G0/G1, but fewer cells at the S phase, which EGR1 knockdown reversed these effects. Furthermore, tumorigenicity analysis revealed that METTL7B promotes tumor growth of GBM cells in vivo. METTL7B contributes to the malignant progression of GBM by inhibiting EGR1 expression. METTL7B and EGR1 may be utilized as the treatment targets for GBM therapy.
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Abbreviations
- GBM:
-
Glioblastoma
- CNS:
-
central nervous system
- TMZ:
-
temozolomide
- SAM:
-
S-adenosyl methionine
- METTL7B:
-
Mammalian methyltransferase-like 7B
- EGR1:
-
early growth response 1
- PDGFA:
-
platelet-derived growth factor subunit A
- CCK-8:
-
Cell Counting Kit-8
- qRT-PCR:
-
Quantitative reverse transcription-PCR
- ANOVA:
-
Analysis of Variance
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LX set up the conceptualization. LX, BP and HW conducted the experiments and YZ, QY and SF conducted formal analysis and investigation. LX and BP finished original drafting preparation. LX finished writing, revising and editing work. All authors have read and approved the manuscript.
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Xu, L., Peng, B., Wu, H. et al. METTL7B contributes to the malignant progression of glioblastoma by inhibiting EGR1 expression. Metab Brain Dis 37, 1133–1143 (2022). https://doi.org/10.1007/s11011-022-00925-6
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DOI: https://doi.org/10.1007/s11011-022-00925-6