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Integrated high-throughput analysis identifies super enhancers associated with chemoresistance in SCLC

Jiarong Bao1,2, Man Li1, Shumei Liang1

  • 1Department of Pathology, Zhujiang Hospital, Southern Medical University, 253 Gongye Road, Guangzhou, 510282, People's Republic of China.

BMC Medical Genomics
|May 24, 2019
PubMed
Abstract

Insights

Super enhancers (SEs) drive chemoresistance in small cell lung cancer. Researchers identified 45 SEs and 12 master transcription factors (TFs) linked to drug resistance, offering new therapeutic targets.

Area of Science:

  • Genomics
  • Molecular Biology
  • Cancer Research

Background:

  • Chemoresistance presents a significant clinical hurdle in treating small cell lung cancer.
  • Super enhancers (SEs), crucial noncoding DNA regulatory elements, play a vital role in tumor evolution and drug resistance.
  • Understanding SE function is critical for advancing cancer therapy.

Purpose of the Study:

  • To identify super enhancers (SEs) associated with chemoresistance in small cell lung cancer.
  • To predict master transcription factors (TFs) regulating these SEs.
  • To elucidate the functional role of SEs and their associated TFs in drug resistance.

Main Methods:

  • Chromatin immunoprecipitation-sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) were employed to identify SEs.
  • Integrated bioinformatics analysis, including MEME chip, predicted master TFs binding to SE sites.
  • Functional validation involved RNA interference, cell counting kit 8 assays, and quantitative real-time reverse transcription polymerase chain reaction.

Main Results:

  • 108 SEs were identified in H69AR cells, with 45 linked to drug resistance.
  • 12 master TFs were predicted to be located in SE regions associated with chemoresistance.
  • Forkhead box P1 (FOXP1), interferon regulatory factor 1 (IRF1), and specificity protein 1 (SP1) were validated for their roles in chemoresistance via SEs.

Conclusions:

  • This study identified a significant number of SEs involved in small cell lung cancer drug resistance.
  • The findings reveal mechanisms by which SEs contribute to chemoresistance.
  • The research provides potential insights for the clinical application of SEs in cancer treatment.
Keywords:
ChemoresistanceSmall cell lung cancerSuper enhancer

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