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MicroRNA-449a delays lung cancer development through inhibiting KDM3A/HIF-1α axis

Shan Hu1, Peng Cao1, Kangle Kong1

  • 1Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Qiaokou District, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei, China.

Journal of Translational Medicine
|May 28, 2021
PubMed
Abstract

Insights

MicroRNA-449a inhibits lung cancer by targeting the KDM3A/HIF-1α pathway. Restoring miR-449a levels suppressed tumor growth, offering a potential therapeutic strategy for lung cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • MicroRNA-449a (miR-449a) exhibits anti-tumor properties in various cancers, including lung cancer.
  • The specific molecular mechanisms underlying miR-449a's role in lung cancer progression require further elucidation.

Purpose of the Study:

  • To investigate the role of miR-449a in lung cancer development.
  • To explore the involvement of the lysine demethylase 3A/hypoxia-induced factor-1α (KDM3A/HIF-1α) axis in miR-449a-mediated lung cancer regulation.

Main Methods:

  • Quantitative analysis of miR-449a, KDM3A, and HIF-1α expression in lung cancer tissues and cell lines.
  • In vitro loss- and gain-of-function assays to assess cellular proliferation, cell cycle, apoptosis, invasion, and migration.
  • In vivo tumor growth monitoring in a mouse model.
  • Verification of molecular interactions between miR-449a, KDM3A, and HIF-1α.

Main Results:

  • Lung cancer tissues and cells showed decreased miR-449a and increased KDM3A and HIF-1α levels.
  • miR-449a directly targets KDM3A, and KDM3A interacts with HIF-1α.
  • Upregulation of miR-449a inhibited lung cancer progression, while its suppression promoted it.
  • KDM3A and HIF-1α upregulation counteracted the anti-tumor effects of miR-449a, and KDM3A promoted cancer cell aggression.

Conclusions:

  • miR-449a exerts anti-tumor effects in lung cancer by suppressing the KDM3A/HIF-1α signaling pathway.
  • The miR-449a/KDM3A/HIF-1α axis represents a potential therapeutic target for lung cancer treatment.
Keywords:
Hypoxia-induced factor-1αLung cancerLysine demethylase 3AMicroRNA-449a

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