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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Down-Regulating the Expression of miRNA-21 Inhibits the Glucose Metabolism of A549/DDP Cells and Promotes Cell Death
Ye Sun1,2, Wenjun Liu3, Qiuyu Zhao4
1Department of Cell Biology, College of Integrated Chinese and Western Medical, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Abstract:
miRNA-21 is a single-stranded non-coding RNA that is highly expressed in a variety of tumor cells. It participates in tumor cell proliferation, metabolism, metastasis, and drug resistance. Here, we tested the potential mechanism of miRNA-21 in cisplatin-resistant non-small cell lung cancer A549/DDP (human lung adenocarcinoma drug-resistant cell line) cells. A549 and A549/DDP RNAs were sequenced to show that miRNA-21 was highly expressed in the latter, and this was verified by qRT-PCR. In addition, we found that miRNA-21 combined with cisplatin can significantly inhibit glycolysis and glycolysis rate-limiting enzyme protein expression in A549/DDP cells. We also found that miRNA-21 combined with cisplatin can promote A549/DDP cell death. Further investigations showed that miRNA-21 combined with cisplatin caused excessive inactivation of the pI3K/AKT/mTOR/HIF-1α signaling pathway in cisplatin-resistant A549/DDP cells. Hence, reduction of the expression of miRNA-21 in combination with cisplatin chemotherapy may effectively improve the therapeutic effect on patients with non-small cell lung cancer, and this may provide a theoretical basis for the treatment of this disease.
Insights
MicroRNA-21 (miRNA-21) is highly expressed in cisplatin-resistant lung cancer cells and promotes drug resistance. Inhibiting miRNA-21 with cisplatin may enhance treatment efficacy by reducing glycolysis and promoting cell death.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNA-21 (miRNA-21) is implicated in various cancers, affecting proliferation, metastasis, and drug resistance.
- Cisplatin resistance is a significant challenge in treating non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To investigate the mechanism of miRNA-21 in cisplatin-resistant A549/DDP cells.
- To evaluate the combined effect of miRNA-21 inhibition and cisplatin on NSCLC cells.
Main Methods:
- RNA sequencing and quantitative real-time PCR (qRT-PCR) to assess miRNA-21 expression.
- Analysis of glycolysis, enzyme activity, and cell death in A549/DDP cells treated with miRNA-21 and cisplatin.
- Investigation of the PI3K/AKT/mTOR/HIF-1α signaling pathway.
Main Results:
- miRNA-21 was significantly upregulated in cisplatin-resistant A549/DDP cells compared to A549 cells.
- Combined treatment with miRNA-21 and cisplatin inhibited glycolysis and reduced key glycolytic enzyme expression.
- The combination therapy promoted A549/DDP cell death and excessively inactivated the PI3K/AKT/mTOR/HIF-1α pathway.
Conclusions:
- miRNA-21 plays a crucial role in cisplatin resistance in NSCLC by influencing glycolysis and cell survival.
- Reducing miRNA-21 expression alongside cisplatin chemotherapy may represent a promising therapeutic strategy for NSCLC.
- This study provides a theoretical basis for targeting miRNA-21 in combination with cisplatin for improved NSCLC treatment outcomes.
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