Related Experiment Video

Updated: Jul 16, 2025

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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CircXRN2 suppresses tumor progression driven by histone lactylation through activating the Hippo pathway in human

Bo Xie1, Juntao Lin1, Xianwu Chen1

  • 1Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, R.P. China.

Molecular Cancer
|September 8, 2023
PubMed
Abstract

Insights

Circular RNA XRN2 (circXRN2) suppresses bladder cancer progression by activating the Hippo pathway and inhibiting histone lactylation. This discovery offers new therapeutic strategies for bladder cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Bladder cancer (BCa) is a prevalent malignancy with a poor prognosis.
  • Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer, but their specific functions in BCa require further elucidation.
  • Histone lactylation is an emerging epigenetic modification implicated in tumorigenesis.

Purpose of the Study:

  • To investigate the role of circXRN2 in bladder cancer progression.
  • To explore the molecular mechanisms by which circXRN2 influences tumor growth, focusing on the Hippo pathway and histone lactylation.
  • To identify potential therapeutic targets for bladder cancer.

Main Methods:

  • RNA immunoprecipitation (RIP) and circRNA sequencing to identify and validate circXRN2.
  • Cellular and in vivo experiments (overexpression/knockdown) to assess circXRN2 function.
  • Co-immunoprecipitation, CUT&Tag, and ChIP assays to elucidate molecular interactions and regulatory roles.
  • Seahorse metabolic analysis to evaluate cellular metabolism.

Main Results:

  • CircXRN2 is downregulated in bladder cancer tissues and cell lines.
  • CircXRN2 inhibits tumor cell proliferation and migration in vitro and in vivo.
  • CircXRN2 negatively regulates glycolysis and lactate production.
  • CircXRN2 prevents LATS1 degradation, activating the Hippo pathway.
  • The circXRN2-Hippo pathway axis inhibits H3K18 lactylation and LCN2 expression, suppressing bladder cancer progression.

Conclusions:

  • CircXRN2 acts as a tumor suppressor in bladder cancer by activating the Hippo pathway and inhibiting H3K18 lactylation-driven tumor progression.
  • The circXRN2-Hippo pathway offers a novel regulatory axis with potential as a therapeutic target for bladder cancer.
Keywords:
Bladder cancerHippo pathwayHistone lactylationTumor progressioncircXRN2

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