MiR-17- 5p/RRM2 regulated gemcitabine resistance in lung cancer A549 cells

Xuan Ma1,2, Tian Fu3, Zhi-Yin Ke1

  • 1Department of Biochemistry and Molecular Biology & Department of Clinical Biochemistry, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, China.

Insights

The miR-17-5p/RRM2 axis regulates gemcitabine resistance in A549 lung cancer cells. Modulating miR-17-5p affects drug sensitivity and cell cycle progression, involving the PTEN/PI3K/AKT pathway.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Gemcitabine is a key chemotherapy drug for non-small cell lung cancer (NSCLC).
  • Acquired gemcitabine resistance in A549 cells poses a significant clinical challenge.
  • MicroRNAs (miRNAs) are increasingly recognized as regulators of drug resistance.

Purpose of the Study:

  • To elucidate the regulatory role of the miR-17-5p/RRM2 axis in gemcitabine resistance of A549 cells.
  • To investigate the underlying molecular mechanisms, including cell cycle and signaling pathways.

Main Methods:

  • Cell viability assays (CCK8, clonogenic assays).
  • Gene expression analysis (RT-qPCR, Western blotting).
  • Cell cycle analysis (flow cytometry).
  • Luciferase reporter assays to confirm miRNA targets.

Main Results:

  • Upregulation of miR-17-5p decreased gemcitabine resistance in A549G+ cells, increasing G1 phase and decreasing S phase.
  • miR-17-5p affected cell cycle proteins (CCNE1, CCNA2, P21) and the PTEN/PI3K/AKT pathway (increased p-PTEN, decreased p-AKT).
  • RRM2 was confirmed as a direct target of miR-17-5p.

Conclusions:

  • The miR-17-5p/RRM2 axis plays a crucial role in modulating gemcitabine resistance in A549 cells.
  • The PTEN/PI3K/AKT signaling pathway is implicated in the miR-17-5p-mediated regulation of gemcitabine resistance.

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