LncRNA MITA1 promotes gefitinib resistance by inducing autophagy in lung cancer cells

Jie Hu1, Shu-Wen Dong1, Yinghua Pei1

  • 1Department of Respiratory and Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.

Insights

Long non-coding RNA MITA1 is upregulated in non-small cell lung cancer (NSCLC) cells resistant to gefitinib. MITA1 promotes gefitinib resistance by suppressing apoptosis and inducing autophagy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-small cell lung cancer (NSCLC) poses a significant global health burden.
  • Gefitinib, a tyrosine kinase inhibitor (TKI), is a standard treatment for advanced NSCLC.
  • Acquired drug resistance limits the long-term efficacy of gefitinib therapy.

Purpose of the Study:

  • To investigate the role of long non-coding RNA (lncRNA) MITA1 in the development of gefitinib resistance in NSCLC.
  • To elucidate the molecular mechanisms underlying MITA1-mediated gefitinib resistance.

Main Methods:

  • Utilized gefitinib-sensitive (HCC827) and resistant (HCC827GR) NSCLC cell lines.
  • Manipulated MITA1 expression using transfection (pcDNA-MITA1, si-MITA1) and assessed gefitinib treatment effects.
  • Evaluated cell viability and apoptosis via MTT and flow cytometry assays.
  • Examined autophagy markers (LC3, Beclin-1, p62) using qRT-PCR, Western blotting, and immunofluorescence.
  • Confirmed findings in the presence of the autophagy inhibitor bafilomycin A1.

Main Results:

  • lncRNA MITA1 was significantly upregulated in gefitinib-resistant NSCLC cells.
  • Overexpression of MITA1 conferred gefitinib resistance by decreasing apoptosis and increasing cell viability.
  • MITA1 induction of autophagy was confirmed through analysis of autophagy markers and validated with an autophagy inhibitor.
  • Upregulated MITA1 was directly correlated with increased autophagy and gefitinib resistance.

Conclusions:

  • lncRNA MITA1 plays a crucial role in the acquisition of gefitinib resistance in NSCLC.
  • MITA1 confers resistance primarily by suppressing apoptosis and promoting autophagy.
  • Targeting MITA1 or its downstream autophagy pathway may represent a therapeutic strategy to overcome gefitinib resistance in NSCLC.

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