DNA methylation provides diagnostic value for meningioma recurrence in clinical practice

Shen, Erica; Leclair, Nathan K.; Herlth, Kristi; Soucy, Melissa; Renzette, Nick; Zhuo, Xinming; Kelly, Kevin; Omerza, Gregory; Onyiuke, Hilary; McNeill, Ian; Wolansky, Leo; Becker, Kevin; Li, Lei; Wu, Qian; Bulsara, Ketan R.

doi:10.1007/s00701-023-05550-5

Cited by 2 publications

(1 citation statement)

References 46 publications

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“…Meningiomas are closely associated with ossi cation and calci cation, and the involvement of bone morphogenetic protein (BMP), insulin-like growth factor-1, endothelin-1, and osteoprotegerin has been investigated, but any function in meningioma cells is still unknown [6]. The new WHO 2021 classi cation scheme of meningiomas added gene and methylation pro les which are strongly correlated with the prognosis [7][8][9][10][11], but how changes in these genes and methylation pro les relate to meningioma metabolism and drug treatment targets remain unclear. This study investigated the involvement of Gremlin2 (GREM2), an inhibitor of BMP signaling, particularly the BMP signaling essential for bone formation, in meningioma growth, senescence, and calci cation via tryptophan metabolism.…”

Section: Introductionmentioning

confidence: 99%

Induced senescence and calcification in anaplastic meningioma

Yokogami,

Watanabe,

Yamashita

et al. 2024

Preprint

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Purpose. Meningiomas are the most common type of brain tumors and are generally benign, but malignant atypical meningiomas and anaplastic meningiomas frequently recur with poor prognosis. The metabolism of meningiomas is little known, so few effective treatment options other than surgery and radiation are available, and the targets for treatment of recurrence are not well defined. The Aim of this paper is to find the therapeutic target. Methods. This study focused on meningioma metabolism and demonstrated that bone morphogenetic protein (BMP) signaling regulates meningioma growth, cellular senescence, and calcification. Results. Inhibitors of BMP receptor (BMPR1A) and forced expression of Gremlin2 (GREM2) shifted tryptophan metabolism from kynurenine/quinolinic acid production to serotonin production in malignant meningiomas, reduced NAD+/NADH production, decreased gene cluster expression involved in oxidative phosphorylation, and caused decrease in ATP. Finally, malignant meningiomas underwent cellular senescence, decreased proliferation, and eventually formed psammoma bodies. We reanalyzed RNA-sequencing data of clinical samples obtained from GEO RNA-seq Experiments Interactive Navigator, a public database, and found that increased expression of GREM2 decreased the expression of genes involved in oxidative phosphorylation, similar to our experimental results. Conclusions. The GREM2-BMPR1A-tryptophan metabolic pathway in meningiomas is a potential new therapeutic target.

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Section: Introductionmentioning

confidence: 99%

Induced senescence and calcification in anaplastic meningioma

Yokogami,

Watanabe,

Yamashita

et al. 2024

Preprint

View full text Add to dashboard Cite

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Inhibition of BMP signaling pathway induced senescence and calcification in anaplastic meningioma

Yokogami,

Watanabe,

Yamashita

et al. 2024

J Neurooncol

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Purpose Meningiomas are the most common type of brain tumors and are generally benign, but malignant atypical meningiomas and anaplastic meningiomas frequently recur with poor prognosis. The metabolism of meningiomas is little known, so few effective treatment options other than surgery and radiation are available, and the targets for treatment of recurrence are not well defined. The Aim of this paper is to find the therapeutic target. Methods The effects of bone morphogenetic protein (BMP) signal inhibitor (K02288) and upstream regulator Gremlin2 (GREM2) on meningioma’s growth and senescence were examined. In brief, we examined as follows: 1) Proliferation assay by inhibiting BMP signaling. 2) Comprehensive analysis of forced expression GREM2.3) Correlation between GREM2 mRNA expression and proliferation marker in 87 of our clinical samples. 4) Enrichment analysis between GREM2 high/low expressed groups using RNA-seq data (42 cases) from the public database GREIN. 5) Changes in metabolites and senescence markers associated with BMP signal suppression. Results Inhibitors of BMP receptor (BMPR1A) and forced expression of GREM2 shifted tryptophan metabolism from kynurenine/quinolinic acid production to serotonin production in malignant meningiomas, reduced NAD + /NADH production, decreased gene cluster expression involved in oxidative phosphorylation, and caused decrease in ATP. Finally, malignant meningiomas underwent cellular senescence, decreased proliferation, and eventually formed psammoma bodies. Reanalyzed RNA-seq data of clinical samples obtained from GREIN showed that increased expression of GREM2 decreased the expression of genes involved in oxidative phosphorylation, similar to our experimental results. Conclusions The GREM2-BMPR1A-tryptophan metabolic pathway in meningiomas is a potential new therapeutic target.

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DNA methylation provides diagnostic value for meningioma recurrence in clinical practice

Cited by 2 publications

References 46 publications

Induced senescence and calcification in anaplastic meningioma

Induced senescence and calcification in anaplastic meningioma

Inhibition of BMP signaling pathway induced senescence and calcification in anaplastic meningioma

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