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CircMYBL1 suppressed acquired resistance to osimertinib in non-small-cell lung cancer

Yaji Li1, Nan Wang1, Yutang Huang1

  • 1Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China.

Cancer Genetics
|April 16, 2024
PubMed

Insights

Circular RNAs (circRNAs) are crucial in acquired resistance to anticancer drugs. Downregulation of circMYBL1 in non-small-cell lung cancer (NSCLC) cells promotes tumor growth, indicating its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Acquired resistance to targeted therapies like osimertinib is a major challenge in non-small-cell lung cancer (NSCLC) treatment.
  • Circular RNAs (circRNAs) are implicated in the development of drug resistance across various cancers.
  • Understanding the role of circRNAs in osimertinib resistance is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To investigate the differential expression profiles of circRNAs in osimertinib-sensitive versus acquired-resistant NSCLC cell lines.
  • To identify specific circRNAs that are altered during the development of osimertinib resistance.
  • To evaluate the functional role of a key differentially expressed circRNA in NSCLC progression.

Main Methods:

  • Development of osimertinib-resistant NSCLC cell lines.
  • RNA sequencing (RNA-Seq) to analyze circRNA expression profiles.
  • Quantitative real-time PCR (qRT-PCR) for validation in cell lines and patient plasma samples.

Main Results:

  • Significant differences in circRNA expression were observed between osimertinib-sensitive and -resistant NSCLC cells.
  • CircMYBL1 (has_circ_0136924) was found to be downregulated in acquired osimertinib-resistant NSCLC.
  • Inhibition of circMYBL1 expression enhanced proliferation, migration, and invasion in sensitive NSCLC cells.

Conclusions:

  • CircMYBL1 downregulation is associated with acquired resistance to osimertinib in NSCLC.
  • CircMYBL1 plays a role in regulating NSCLC cell proliferation, migration, and invasion.
  • CircMYBL1 represents a potential novel molecular biomarker and therapeutic target for osimertinib-resistant NSCLC.
Keywords:
Acquired resistanceNon-small-cell lung cancerOsimertinibRNA sequencingcircRNA

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