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MiR-140-3p Improves Sensitivity to Docetaxel by Suppressing PD-L1/ABCG2/MVP Expression in Lung Adenocarcinoma
Minji Kwon1, Dayeon Lim1, Jayeon Park1
1Department of Medical Sciences, Graduate School, Soonchunhyang University, Asan, Republic of Korea.
Background/Aim:
Lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC) accounts for the majority of non-small cell lung cancer (NSCLC), and overexpression of programmed death ligand 1 (PD-L1) in these cells is known to induce tumor immune evasion or drug resistance. However, detailed studies are needed to determine whether microRNAs (miRNAs) that reduce PD-L1 expression can suppress drug resistance in NSCLC.
Materials And Methods:
Kaplan Meier plotter and Receiver Operating Characteristic plotter were used to determine the effect of specific miRNAs on survival and chemotherapy response in NSCLC patients. Cell viability, colony formation and invasion assays, and qPCR analyses were also performed.
Results:
The expression of miRNA-140-3p (miR-140-3p) was lower in LUAD patients, compared to the normal group, and low expression of miR-140-3p was associated with poor survival of LUAD patients, but not in LUSC. The miR-140-3p mimic inhibited proliferation, colony formation, and invasion of LUAD cells. Interestingly, the expression of miR-140-3p was significantly lower in the group of LUAD patients who did not respond to docetaxel. In LUAD cells, combined treatment with miR-140-3p and docetaxel significantly reduced cell viability as well as the expression of ABCG2 and MVP, genes associated with drug resistance, compared to either treatment alone. Additionally, combined injection of miR-140-3p mimic and docetaxel significantly inhibited tumor growth compared to treatment with docetaxel alone.
Conclusion:
These results suggest that the high expression of miR-140-3p in LUAD is correlated with good patient prognosis and may contribute to the treatment of LUAD, especially by increasing responsiveness to docetaxel.
Insights
MicroRNA-140-3p (miR-140-3p) may improve lung adenocarcinoma (LUAD) treatment outcomes. Low miR-140-3p predicts poor survival and docetaxel resistance, but its restoration enhances drug sensitivity and inhibits tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), often overexpresses programmed death ligand 1 (PD-L1), contributing to immune evasion and drug resistance.
- The role of specific microRNAs (miRNAs) in modulating PD-L1 expression and influencing drug resistance in NSCLC requires further investigation.
Purpose of the Study:
- To investigate the potential of miRNAs, specifically miRNA-140-3p (miR-140-3p), in overcoming drug resistance in non-small cell lung cancer (NSCLC).
- To determine the correlation between miR-140-3p expression levels, patient prognosis, and response to chemotherapy in LUAD and LUSC.
Main Methods:
- Utilized Kaplan-Meier plotter and Receiver Operating Characteristic plotter to analyze miRNA expression, patient survival, and chemotherapy response in NSCLC.
- Performed in vitro assays including cell viability, colony formation, and invasion assays, alongside quantitative real-time PCR (qPCR) to assess miR-140-3p function in LUAD cells.
- Evaluated the combined effect of miR-140-3p mimic and docetaxel on LUAD cell viability, drug resistance gene expression (ABCG2, MVP), and tumor growth in vivo.
Main Results:
- Lower miR-140-3p expression was observed in LUAD patients, correlating with poor survival, but not significantly in LUSC.
- miR-140-3p mimic suppressed LUAD cell proliferation, colony formation, and invasion.
- Significantly lower miR-140-3p expression was found in LUAD patients unresponsive to docetaxel.
- Combined miR-140-3p and docetaxel treatment reduced LUAD cell viability and expression of drug resistance genes (ABCG2, MVP) more effectively than either treatment alone.
- Co-administration of miR-140-3p mimic and docetaxel significantly inhibited tumor growth compared to docetaxel alone.
Conclusions:
- Elevated miR-140-3p expression in LUAD is associated with a favorable prognosis.
- miR-140-3p holds therapeutic potential for LUAD treatment, particularly in enhancing patient responsiveness to docetaxel chemotherapy.
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