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MiR-200b regulates autophagy associated with chemoresistance in human lung adenocarcinoma

Banzhou Pan1, Bing Feng1, Yitian Chen1

  • 1Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China.

Oncotarget
|September 30, 2015
PubMed

Insights

MicroRNA-200b (miR-200b) downregulation and autophagy-associated gene 12 (ATG12) upregulation promote chemoresistance in lung adenocarcinoma (LAD). Restoring miR-200b enhances chemosensitivity by inhibiting autophagy.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • Chemoresistance is a significant challenge in treating human lung adenocarcinoma (LAD).
  • Aberrant autophagy is implicated in the development of chemoresistance in LAD.
  • Understanding the molecular mechanisms underlying chemoresistance is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the relationship between microRNA-200b (miR-200b) and autophagy-associated gene 12 (ATG12) in LAD chemoresistance.
  • To elucidate the role of the miR-200b/ATG12 axis in regulating autophagy and chemosensitivity in LAD.
  • To explore the potential of targeting this pathway for overcoming chemoresistance.

Main Methods:

  • Comparative analysis of miR-200b and ATG12 expression in docetaxel-resistant and sensitive LAD cell lines and tissue samples.
  • Luciferase reporter assays to confirm direct targeting of ATG12 by miR-200b.
  • In vitro and in vivo experiments to assess the impact of modulating miR-200b and ATG12 on autophagy and chemosensitivity.

Main Results:

  • An inverse correlation was observed between miR-200b and ATG12 expression in LAD cells and tissues.
  • miR-200b was confirmed to directly target ATG12 in LAD.
  • Downregulation of ATG12 by miR-200b inhibited autophagy and enhanced chemosensitivity in vitro and in vivo.

Conclusions:

  • LAD chemoresistance is associated with decreased miR-200b and increased ATG12 expression.
  • The miR-200b/ATG12 network plays a critical role in modulating autophagy and influencing chemoresistance in LAD.
  • Targeting the miR-200b/ATG12 pathway offers a potential therapeutic strategy to enhance the efficacy of chemotherapy for LAD.
Keywords:
ATG12autophagychemoresistancehuman lung adenocarcinomamiR-200b

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