Related Experiment Video

Updated: Jun 10, 2025

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations
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Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations

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The interaction between UBR7 and PRMT5 drives PDAC resistance to gemcitabine by regulating glycolysis and immune

Maoxiao Feng1, Qinlian Jiao1, Yidan Ren1

  • 1Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.

Cell Death & Disease
|October 18, 2024
PubMed

Insights

Researchers identified the UBR7-PRMT5 axis as crucial for gemcitabine resistance in pancreatic cancer. Targeting this axis may overcome drug resistance and improve pancreatic cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genomics

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) is a lethal digestive tract malignancy.
  • Gemcitabine resistance significantly limits treatment efficacy in advanced pancreatic cancer.
  • Mechanisms underlying gemcitabine resistance in PDAC remain largely unknown.

Purpose of the Study:

  • To investigate the molecular mechanisms of gemcitabine resistance in pancreatic cancer.
  • To identify key genes and pathways involved in mediating gemcitabine resistance.
  • To explore potential therapeutic targets for overcoming gemcitabine resistance in PDAC.

Main Methods:

  • Utilized ATAC-seq, ChIP-seq, and RNA-seq on a patient-derived tumor xenograft (PDX) model of pancreatic cancer.
  • Compared chromatin accessibility and gene expression in gemcitabine-sensitive and resistant PDX models.
  • Investigated the functional role of UBR7 and its interaction with PRMT5 in pancreatic cancer cells.

Main Results:

  • Discovered significant alterations in chromatin accessibility associated with gemcitabine resistance.
  • Identified UBR7 as a critical mediator of gemcitabine resistance in PDAC.
  • Demonstrated that UBR7 depletion enhances pancreatic carcinogenesis and immunosuppression by increasing PRMT5 stability and promoting glycolysis.
  • Showed that a PRMT5 inhibitor (DS-437) effectively reduces gemcitabine resistance.

Conclusions:

  • The UBR7-PRMT5 signaling axis is a key metabolic regulator in pancreatic ductal adenocarcinoma.
  • This axis plays a pivotal role in mediating gemcitabine resistance.
  • Targeting the UBR7-PRMT5 axis presents a promising therapeutic strategy for overcoming gemcitabine resistance in PDAC.

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