Related Experiment Video

Updated: Jun 10, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
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Published on: January 7, 2019

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Doxorubicin resistance involves modulation of interferon signaling, transcriptional bursting, and gene co-expression

Pawel Trzaskoma1, SeolKyoung Jung1, Yuka Kanno1

  • 1National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.

Neoplasia (New York, N.Y.)
|October 15, 2024
PubMed

Insights

Doxorubicin treatment in colon cancer cells reveals distinct cell populations. Upregulated genes linked to the unphosphorylated ISGF3 (U-ISGF3) transcription factor correlate with chemoresistance, suggesting new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Chemotherapy, like doxorubicin (DOX), is vital for cancer treatment but can cause drug resistance and senescence.
  • Understanding cellular responses to chemotherapy is crucial for improving treatment efficacy.

Purpose of the Study:

  • To investigate transcriptomic changes in human colon cancer cells after doxorubicin (DOX) treatment.
  • To identify specific cell populations and molecular pathways associated with chemoresistance.

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) to analyze transcriptional profiles of individual cells.
  • Mathematical modeling to study transcription kinetics.
  • Gene expression correlation analysis.

Main Results:

  • Identified distinct cell clusters with differential gene expression, including those involved in cell cycle regulation and interferon (IFN) signaling.
  • DOX-persisting proliferating cells showed increased expression of genes linked to the unphosphorylated ISGF3 (U-ISGF3) transcription factor.
  • HSH2D, a poor prognostic marker, was upregulated in surviving cells and correlated with U-ISGF3-related genes; transcription of these genes increased.

Conclusions:

  • U-ISGF3-related genes and the JAK/STAT pathway are implicated in doxorubicin resistance in colon cancer.
  • Altered gene co-expression patterns in surviving cells may contribute to chemoresistance.
  • Targeting U-ISGF3-related genes presents a potential strategy to overcome chemoresistance.
Keywords:
ChemoresistanceColorectal cancerJAK/STATMathematical modelingTranscriptional burstingscRNA-Seq

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