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MicroRNA-99a Suppresses Breast Cancer Progression by Targeting FGFR3

Xinghua Long1, Yu Shi1, Peng Ye1

  • 1Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.

Frontiers in Oncology
|February 11, 2020
PubMed

Insights

MicroRNA-99a (miR-99a) acts as a tumor suppressor in breast cancer by inhibiting cell proliferation and migration. It targets FGFR3, suggesting a potential therapeutic target for breast cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) play critical roles in cancer, functioning as oncogenes or tumor suppressors.
  • Dysregulation of miRNAs is common in breast cancer, affecting various cellular processes.

Purpose of the Study:

  • To investigate the role of miR-99a in breast cancer cell biological processes.
  • To identify the molecular targets and regulatory mechanisms of miR-99a in breast cancer.

Main Methods:

  • Breast cancer cell transfection with miR-99a lentivirus.
  • In vitro functional assays (proliferation, invasion, migration).
  • In vivo tumor xenograft experiments.
  • Dual luciferase reporter assays to confirm direct targeting.
  • Analysis of miR-99a and FGFR3 expression in breast tumors.
  • FGFR3 silencing experiments.
  • Deep sequencing and network construction (circRNA/miRNA, lncRNA/miRNA, miRNA-mRNA).

Main Results:

  • miR-99a overexpression significantly inhibited breast cancer cell proliferation, invasion, and migration in vitro and in vivo.
  • miR-99a directly targets Fibroblast Growth Factor Receptor 3 (FGFR3) by binding to its 3' UTR.
  • miR-99a was downregulated, while FGFR3 was upregulated in breast tumors.
  • FGFR3 silencing mimicked the inhibitory effects of miR-99a on cancer cell growth and metastasis.
  • Transcriptome-wide analysis revealed miR-99a regulates multiple signaling pathways.

Conclusions:

  • The miR-99a/FGFR3 axis is a critical regulator of tumor progression in breast cancer.
  • miR-99a functions as a tumor suppressor by targeting FGFR3.
  • This axis represents a potential therapeutic target for breast cancer treatment.
Keywords:
FGFR3breast cancercircRNAdeep sequencinglncRNAmetastasismiR-99a

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