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.

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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