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Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines

Tianxiang Chen1,2, Jizhuang Luo3, Yu Gu4

  • 1Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Thoracic Cancer
|March 19, 2019
PubMed
Abstract

Insights

Acquired resistance to Osimertinib (AZD9291) in non-small cell lung cancer is inevitable. This study identifies circular RNAs (circRNAs) as potential targets for overcoming AZD9291 resistance in NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Osimertinib (AZD9291) is a third-generation EGFR-tyrosine kinase inhibitor used for non-small cell lung cancer (NSCLC) with EGFR mutations.
  • Acquired resistance to AZD9291 is a significant clinical challenge, necessitating research into resistance mechanisms.
  • Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development and progression.

Purpose of the Study:

  • To investigate the role of circRNAs in acquired resistance to AZD9291 in NSCLC.
  • To identify differentially expressed circRNAs in AZD9291-resistant NSCLC cell lines.
  • To explore circRNAs as potential therapeutic targets for overcoming AZD9291 resistance.

Main Methods:

  • Established AZD9291-resistant NSCLC cell lines (H1975/AZDR and HCC827/AZDR) by gradually increasing drug concentration.
  • Utilized circRNA microarray analysis to compare circRNA expression profiles between sensitive and resistant cell lines.
  • Validated differentially expressed circRNAs using quantitative reverse transcription PCR and performed bioinformatic analysis.

Main Results:

  • Successfully established AZD9291-resistant NSCLC cell lines with significantly enhanced invasion ability and resistance to Osimertinib.
  • Microarray analysis identified a large number of differentially expressed circRNAs (15,504), with 7966 upregulated and 7538 downregulated.
  • Bioinformatic analysis predicted miRNA interactions and indicated that dysregulated circRNAs are involved in cancer-related pathways.

Conclusions:

  • Circular RNAs play a crucial role in the development of AZD9291 resistance in non-small cell lung cancer.
  • Dysregulated circRNAs represent promising molecular targets for developing novel gene therapies to overcome Osimertinib resistance.
  • Further research into circRNA-mediated mechanisms is warranted for effective NSCLC treatment strategies.
Keywords:
AZD9291NSCLCcircular RNAmicroarrayresistance

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