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Updated: Mar 22, 2026
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Genome-wide profiling of long non-coding RNA expression patterns in the EGFR-TKI resistance of lung adenocarcinoma by
Ying Wu1, Dan-Dan Yu1, Yong Hu2
1The First Clinical School of Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China.
Abstract:
Mutations in the epidermal growth factor receptor (EGFR) make lung adenocarcinoma cells sensitive to EGFR tyrosine kinase inhibitors (TKIs). Long-term cancer therapy may cause the occurrence of acquired resistance to EGFR TKIs. Long non-coding RNAs (lncRNAs) play important roles in tumor formation, tumor metastasis and the development of EGFR-TKI resistance in lung cancer. To gain insight into the molecular mechanisms of EGFR-TKI resistance, we generated an EGFR-TKI-resistant HCC827-8-1 cell line and analyzed expression patterns by lncRNA microarray and compared it with its parental HCC827 cell line. A total of 1,476 lncRNA transcripts and 1,026 mRNA transcripts were dysregulated in the HCC827‑8-1 cells. The expression levels of 7 chosen lncRNAs were validated by real-time quantitative PCR. As indicated by functional analysis, several groups of lncRNAs may be involved in the bio-pathways associated with EGFR-TKI resistance through their cis- and/or trans‑regulation of protein-coding genes. Thus, lncRNAs may be used as novel candidate biomarkers and potential targets in EGFR-TKI therapy in the future.
Insights
Long non-coding RNAs (lncRNAs) are implicated in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in lung cancer. Dysregulated lncRNAs may serve as biomarkers and therapeutic targets for overcoming EGFR-TKI resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Activating mutations in the epidermal growth factor receptor (EGFR) drive lung adenocarcinoma sensitivity to EGFR tyrosine kinase inhibitors (TKIs).
- Acquired resistance to EGFR TKIs is a significant challenge in long-term lung cancer therapy.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development and drug resistance.
Purpose of the Study:
- To investigate the molecular mechanisms underlying acquired resistance to EGFR TKIs.
- To identify dysregulated long non-coding RNAs (lncRNAs) in EGFR-TKI-resistant lung adenocarcinoma cells.
- To explore the potential of lncRNAs as biomarkers and therapeutic targets for EGFR-TKI resistance.
Main Methods:
- Generation of an EGFR-TKI-resistant cell line (HCC827-8-1) from a parental lung adenocarcinoma cell line (HCC827).
- lncRNA microarray analysis to compare expression profiles between resistant and parental cells.
- Validation of selected lncRNA expression levels using real-time quantitative PCR.
- Functional analysis to infer the involvement of lncRNAs in relevant biological pathways.
Main Results:
- A total of 1,476 lncRNA transcripts and 1,026 mRNA transcripts were found to be dysregulated in the EGFR-TKI-resistant HCC827-8-1 cells compared to HCC827 cells.
- Expression levels of seven specific lncRNAs were validated.
- Functional analysis suggested that several lncRNAs may regulate protein-coding genes through cis- and/or trans-acting mechanisms, potentially contributing to EGFR-TKI resistance.
Conclusions:
- lncRNAs are significantly dysregulated in EGFR-TKI-resistant lung adenocarcinoma.
- These dysregulated lncRNAs may play crucial roles in the development of EGFR-TKI resistance.
- lncRNAs represent promising novel candidate biomarkers and potential therapeutic targets for overcoming EGFR-TKI resistance in lung cancer.
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