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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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HOTAIR induces EGFR-TKIs resistance in non-small cell lung cancer through epithelial-mesenchymal transition

Qi Wang1, Xuefei Li2, Shengxiang Ren1

  • 1Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, 200433, PR China.

Lung Cancer (Amsterdam, Netherlands)
|July 20, 2020
PubMed
Abstract

Insights

HOTAIR, a long non-coding RNA, is down-regulated in non-small cell lung cancer (NSCLC) resistant to EGFR-TKIs. Its restoration can re-sensitize cells to treatment, suggesting HOTAIR as a predictive biomarker for EGFR-TKI resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Aberrant expression of HOTAIR, a long non-coding RNA, is linked to cancer progression, invasion, metastasis, and chemo-resistance.
  • Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs) are crucial in treating non-small cell lung cancer (NSCLC), but resistance remains a significant clinical challenge.

Purpose of the Study:

  • To investigate the role of HOTAIR in the development of resistance to EGFR-TKIs in NSCLC.
  • To determine if HOTAIR expression levels can serve as a predictive biomarker for EGFR-TKI resistance in NSCLC patients.

Main Methods:

  • Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to measure HOTAIR expression in NSCLC cell lines and patient tumor tissues.
  • Cell proliferation and apoptosis were assessed using CCK-8 and flow cytometry assays.
  • Epithelial-mesenchymal transition (EMT) protein expression was evaluated by western blot.

Main Results:

  • HOTAIR was significantly down-regulated in NSCLC cells and patients exhibiting primary or acquired resistance to EGFR-TKIs.
  • High HOTAIR expression correlated with longer progression-free survival (PFS) in EGFR-TKI-sensitive NSCLC tumors.
  • Overexpression of HOTAIR restored sensitivity to gefitinib in resistant NSCLC cells (PC9/R, H1299, A549) by inducing apoptosis and activating EMT.

Conclusions:

  • HOTAIR expression is associated with both primary and acquired resistance to EGFR-TKIs in NSCLC.
  • HOTAIR regulates cell proliferation by modulating apoptosis and EMT, positioning it as a potential biomarker for predicting EGFR-TKI resistance.
Keywords:
Drug resistanceEGFR-TKIsEpithelial-mesenchymal transitionHOTAIRNon-small cell lung cancer

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