Long Noncoding RNA LINC01116 Contributes to Gefitinib Resistance in Non-small Cell Lung Cancer through Regulating
He Wang1, Binbin Lu2, Shengnan Ren1
1Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, People's Republic of China; Department of Oncology, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211166, People's Republic of China.
Molecular Therapy. Nucleic Acids
|December 17, 2019
Summary
Long non-coding RNA LINC01116 promotes gefitinib resistance in non-small cell lung cancer (NSCLC) by upregulating IFI44. Downregulating LINC01116 may overcome resistance to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) in NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are first-line treatments for non-small cell lung cancer (NSCLC).
- Acquired resistance to TKIs like gefitinib poses a significant challenge to long-term patient survival and treatment efficacy.
- Understanding the molecular mechanisms underlying TKI resistance is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the role of the long non-coding RNA (lncRNA) LINC01116 in gefitinib resistance in NSCLC.
- To elucidate the underlying molecular mechanism by which LINC01116 influences gefitinib sensitivity.
- To explore LINC01116 as a potential therapeutic target for overcoming TKI resistance.
Main Methods:
- Analysis of LINC01116 expression in gefitinib-resistant NSCLC cells and tissues.
- Loss- and gain-of-function assays to assess the impact of LINC01116 on gefitinib resistance.
- Investigation of the relationship between LINC01116 and IFI44 expression.
- In vivo studies to evaluate the effect of LINC01116 downregulation on gefitinib sensitivity.
Main Results:
- LINC01116 was found to be upregulated in gefitinib-resistant NSCLC cells and tissues.
- Downregulation of LINC01116 sensitized NSCLC cells to gefitinib, while its overexpression conferred resistance.
- LINC01116 silencing increased IFI44 expression, and IFI44 overexpression reversed gefitinib resistance.
- LINC01116 affects gefitinib resistance partly through regulating IFI44 expression.
- Downregulation of LINC01116 enhanced gefitinib sensitivity in vivo.
Conclusions:
- LINC01116 plays a critical role in mediating gefitinib resistance in NSCLC.
- The mechanism involves LINC01116 regulating IFI44 expression, thereby influencing TKI sensitivity.
- LINC01116 represents a potential novel therapeutic target for overcoming TKI resistance in NSCLC patients.
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