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YBX1 is required for maintaining PD-L1 expression in intrahepatic cholangiocarcinoma by regulating STAT1 stability in an m5C-dependent manner

  • 0Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China; State Key Laboratory of Antiviral Drugs, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Gene Hospital of Henan Province, Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Hepatobiliary & Pancreatic Diseases International : Hbpd Int +

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June 1, 2025

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June 1, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Y-box binding protein 1 (YBX1) promotes intrahepatic cholangiocarcinoma (ICC) by suppressing T-cell responses. It enhances STAT1 translation via m5C binding, activating the STAT1/PD-L1 pathway, indicating YBX1 as a therapeutic target for ICC immunotherapy.

Area Of Science

  • Oncology
  • Molecular Biology
  • Immunology

Background

  • Intrahepatic cholangiocarcinoma (ICC) is a prevalent primary liver cancer.
  • Y-box binding protein 1 (YBX1) is implicated in tumor progression, but its role in ICC requires further elucidation.
  • Understanding YBX1's function is crucial for developing novel ICC immunotherapies.

Purpose Of The Study

  • To investigate the function and regulatory mechanisms of YBX1 in ICC.
  • To assess the potential of YBX1 as a target for ICC immunotherapy.

Main Methods

  • Analysis of YBX1 expression in ICC using immunohistochemistry and public databases (TCGA, GEO).
  • In vitro and in vivo studies involving YBX1 knockdown and overexpression to evaluate antitumor T-cell responses.
  • Mechanistic studies using Actinomycin D, RNA immunoprecipitation, and m5C RNA immunoprecipitation assays.
  • Immunofluorescence validation in clinical ICC specimens.

Main Results

  • Elevated YBX1 expression in ICC correlates with poor patient outcomes.
  • YBX1 suppresses antitumor T-cell responses, thereby promoting tumor progression.
  • YBX1 acts as an m5C reader, enhancing STAT1 translation and activating the STAT1/PD-L1 pathway.
  • Clinical data confirms a strong association between YBX1, STAT1, and PD-L1 levels in ICC.

Conclusions

  • YBX1 regulates STAT1 stability in an m5C-dependent manner within ICC.
  • YBX1 maintains PD-L1 expression, contributing to the tumor microenvironment.
  • Targeting YBX1 may represent a promising strategy for ICC immunotherapy.

Keywords:

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