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Updated: Feb 7, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

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KMT2C Loss Promotes NF2-Wildtype Meningioma Progression and Ferroptosis Sensitivity via Epigenetic Repression of

Liuchao Zhang1, Yangfan Ye1, Wei Gu1

  • 1Department of Neurosurgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, P. R. China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 5, 2026
PubMed

Insights

Loss of KMT2C, a key epigenetic regulator, drives aggressive high-grade meningiomas by suppressing NF2 transcription and inactivating Hippo signaling. Restoring histone acetylation with TSA suppressed tumor growth, offering new therapeutic avenues.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • High-grade meningiomas are aggressive brain tumors with limited treatment options.
  • While NF2 mutations drive many meningiomas, mechanisms in NF2-intact tumors are unclear.
  • KMT2 family members are implicated in cancers, but their role in meningioma is unknown.

Purpose of the Study:

  • Investigate the role of KMT2C in high-grade meningioma pathogenesis.
  • Elucidate the molecular mechanisms by which KMT2C loss affects tumor progression.
  • Identify potential therapeutic targets for NF2-wild-type meningiomas.

Main Methods:

  • Analysis of KMT2C expression in high-grade meningiomas.
  • In vitro studies using meningioma cells to assess KMT2C loss effects on proliferation, invasion, and signaling pathways.
  • Assessment of histone acetylation (H3K27ac) and NF2 transcription.
  • Pharmacological intervention using Trichostatin A (TSA), a histone deacetylase inhibitor.

Main Results:

  • KMT2C expression is significantly reduced in high-grade meningiomas.
  • KMT2C loss promotes meningioma cell proliferation and invasion in NF2-wild-type cells.
  • KMT2C deficiency suppresses NF2 transcription, inactivates Hippo signaling, and increases sensitivity to ferroptosis.
  • KMT2C loss impairs CBP/EP300 acetyltransferase activity, reducing H3K27ac and silencing NF2.
  • TSA treatment suppressed tumor growth by restoring histone acetylation.

Conclusions:

  • KMT2C is a critical epigenetic regulator in high-grade meningiomas, linking histone acetylation to NF2-Hippo pathway activity and ferroptosis.
  • Loss of KMT2C contributes to meningioma progression by epigenetic silencing of NF2.
  • Epigenetic modulation and ferroptosis induction represent promising therapeutic strategies for KMT2C-deficient meningiomas.
Keywords:
KMT2CNF2–Hippo signalingferroptosishistone acetylationmeningioma

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