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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Genomic analysis of drug resistant small cell lung cancer cell lines by combining mRNA and miRNA expression profiling
Yitian Chen1,2, Xiang Yang1, Yichen Xu2
1Department of Medical Oncology, Jinling Hospital, Second Military Medical University, Nanjing, Jiangsu 210002, P.R. China.
Abstract:
Etoposide (VP16) combined with cisplatin (DDP), as the first-line chemotherapy for small cell lung cancer (SCLC), regularly confers drug resistance. The present study applied complementary (c)DNA and micro (mi)RNA microarray to identify gene and miRNA expression profiles associated with multidrug resistance (MDR) in SCLC. The VP16/DDP (VP16 combined with DDP) resistant SCLC H446/EP cell line was derived from the parental H446 cell line by continuous exposure to increasing concentrations of etoposide and cisplatin. The mRNA and miRNA expression profiles between the resistant and parental SCLC cells were analyzed by Phalanx OneArray™ mRNA and miRNA microarray, and the results were confirmed by quantitative polymerase chain reaction. The expression levels of 75 genes were downregulated whilst 40 genes were upregulated in the H446/EP cell line compared with the H446 cell line. The expression levels of 16 miRNAs were upregulated whilst 15 were downregulated in the H446/EP cell line compared with the H446 cell line. Expression profile studies indicate that the particular mRNA and miRNA alteration demonstrated in MDR of SCLC may provide potential biomolecular targets for MDR reversion.
Insights
Drug resistance in small cell lung cancer (SCLC) treated with etoposide and cisplatin is a challenge. This study identified specific gene and microRNA expression changes in resistant SCLC cells, offering potential targets for overcoming multidrug resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- First-line chemotherapy for small cell lung cancer (SCLC) using etoposide (VP16) and cisplatin (DDP) often leads to multidrug resistance (MDR).
- Understanding the molecular mechanisms underlying MDR in SCLC is crucial for developing effective treatment strategies.
Purpose of the Study:
- To identify gene and microRNA (miRNA) expression profiles associated with etoposide/cisplatin resistance in SCLC.
- To explore potential molecular targets for reversing MDR in SCLC.
Main Methods:
- Development of a VP16/DDP-resistant SCLC cell line (H446/EP) from a parental cell line (H446).
- Application of complementary DNA (cDNA) and miRNA microarray analysis to compare gene and miRNA expression between resistant and parental SCLC cells.
- Validation of microarray results using quantitative polymerase chain reaction (qPCR).
Main Results:
- Significant alterations in gene expression were observed, with 75 genes downregulated and 40 genes upregulated in the resistant H446/EP cells compared to H446 cells.
- Distinct miRNA expression changes were detected, including 16 upregulated and 15 downregulated miRNAs in the H446/EP cells.
- These expression profile changes provide insights into the molecular basis of MDR in SCLC.
Conclusions:
- The identified mRNA and miRNA expression alterations in VP16/DDP-resistant SCLC cells represent potential biomarkers.
- These molecular changes may serve as therapeutic targets for overcoming multidrug resistance in small cell lung cancer.
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