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Updated: Feb 6, 2026

High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
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Endogenous HIF2A reporter systems for high-throughput functional screening

M Nazhif Zaini1, Saroor A Patel1, Saiful E Syafruddin1,2

  • 1MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Box 197, Biomedical Campus, Cambridge, CB2 0XZ, United Kingdom.

Scientific Reports
|August 15, 2018
PubMed

Insights

Researchers developed new reporter systems to study HIF2A, a key factor in kidney cancer. These tools enable high-throughput screening to understand cancer-specific gene activity and develop new therapies.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Tissue-specific gene expression dictates biological functions and diseases like cancer.
  • Understanding the molecular basis of transcriptional specificity is crucial for developing targeted therapies.
  • Hypoxia-inducible factor 2-alpha (HIF2A) is a significant driver of renal oncogenesis.

Purpose of the Study:

  • To develop novel experimental reporter systems for interrogating endogenous HIF2A expression.
  • To assess the compatibility of these reporter systems with high-throughput screening.
  • To investigate the regulatory mechanisms controlling cancer-specific transcriptional traits.

Main Methods:

  • Development of novel reporter systems for endogenous HIF2A expression analysis.
  • Utilizing a focused CRISPR-Cas9 library targeting chromatin regulators.
  • Employing high-throughput screening methodologies.

Main Results:

  • Demonstrated the utility of reporter systems for studying endogenous HIF2A expression.
  • Confirmed the compatibility of reporter systems with high-throughput screening approaches.
  • Identified potential redundancy in the regulation of cancer type-specific transcriptional traits.

Conclusions:

  • Novel reporter systems provide a powerful tool for dissecting transcriptional programs in cancer.
  • These systems facilitate large-scale mechanistic studies of cancer phenotypes.
  • The findings pave the way for developing novel therapeutic strategies targeting transcriptional drivers in cancer.

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